The BDNF secreted by immune cells is bioactive, as it supports neuronal survival in vitro.;Brain-derived neurotrophic factor (BDNF) was found to promote the survival of Ell 7 rat embryo septal cholinergic neurons in culture, as assessed by a histochemical stain for acetylcholinesterase (AChE);Thus, the survival action of NGF and BDNF against STS-induced neurotoxicity was mediated by the activation of PI3K/Akt signaling through the Trk receptor.;In explants treated for 7 days, the actions of NT-4/5 were similar to those of brain-derived neurotrophic factor (BDNF)- with either neurotrophin, nearly twice as many RGCs survived and there was a two- to threefold increase in the number of neurites formed by RGCs.
Thus, the survival action of NGF and BDNF against STS-induced neurotoxicity was mediated by the activation of PI3K/Akt signaling through the Trk receptor.;Basic fibroblast growth factor (bFGF), nerve growth factor (NGF), and insulin-like growth factors (IGF-I and IGF-II) each protected neurons against iron-induced damage.
Cultures treated with NT-3 prior to exposure showed reduced cell death compared to untreated control or GDNF-treated cultures.
In explants treated for 7 days, the actions of NT-4/5 were similar to those of brain-derived neurotrophic factor (BDNF)- with either neurotrophin, nearly twice as many RGCs survived and there was a two- to threefold increase in the number of neurites formed by RGCs.
In embryonic midbrain cultures, recombinant human GDNF promoted the survival and morphological differentiation of dopaminergic neurons and increased their high-affinity dopamine uptake.
Treatment of these cultures with acidic fibroblast growth factor (aFGF) or basic fibroblast growth factor (bFGF) increased the number of surviving tyrosine hydroxylase-immunoreactive (TH-IR) neurons by 90-110% [corrected] at 8 d in vitro in a dose-dependent manner.;These data show that both SF/HGF and FGF-1 protect cerebellar granule neurons against excitotoxicity with similar potency in a PI3-K/Akt-dependent and MAP-kinase/CREB-independent manner.
In the present study, EGF was found to enhance survival and process outgrowth of primary cultures of subneocortical telencephalic neurons of neonatal rat brain in a dose-dependent manner.;Epidermal growth factor (EGF) produced a small increase in dopamine uptake by mesencephalic cells and stimulated cell proliferation in all culture types.
Cultured cerebellar granule neurons die by apoptosis when switched from a medium containing an elevated level of potassium (K+) to one with lower K+ (5 mM). Death resulting from the lowering of K+ can be prevented by insulin-like growth factor (IGF-1).;Insulin and the insulin-like growth factors I and II stimulated transmitter-specific differentiation and cell proliferation in all culture types.
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Continuous PDGF-BB treatment of primary rat brain cell cultures resulted in outgrowth of neurites and prolonged survival.;The effects of i.c.v. infused platelet-derived growth factor and brain-derived neurotrophic factor on cell genesis, as assessed with bromodeoxyuridine (BrdU) incorporation, were studied in adult rats with unilateral 6-hydroxydopamine lesions. Both growth factors increased the numbers of newly formed cells in the striatum and substantia nigra to an equal extent following 10 days of treatment.;PDGF-BB but not PDGF-AA reduced the progressive loss of tyrosine hydroxylase- (TH)-positive neurons in rat and human cell cultures.
VEGF (>10 ng/ml) stimulated 5-bromo-2a-deoxyuridine (BrdUrd) incorporation into cells that expressed immature neuronal marker proteins and increased cell number in cultures by 20–30%.;Here we report that VEGF(165) has neurotrophic actions on cultured adult mouse superior cervical ganglia (SCG) and dorsal root ganglia (DRG), measured as axonal outgrowth.;VEGF was found to stimulate axonal outgrowth from DRG, both by an action on the growing axons and the nerve cell bodies.
VEGF (>10 ng/ml) stimulated 5-bromo-2a-deoxyuridine (BrdUrd) incorporation into cells that expressed immature neuronal marker proteins and increased cell number in cultures by 20–30%.;Here we report that VEGF(165) has neurotrophic actions on cultured adult mouse superior cervical ganglia (SCG) and dorsal root ganglia (DRG), measured as axonal outgrowth.;VEGF was found to stimulate axonal outgrowth from DRG, both by an action on the growing axons and the nerve cell bodies.
VEGF (>10 ng/ml) stimulated 5-bromo-2a-deoxyuridine (BrdUrd) incorporation into cells that expressed immature neuronal marker proteins and increased cell number in cultures by 20–30%.;Here we report that VEGF(165) has neurotrophic actions on cultured adult mouse superior cervical ganglia (SCG) and dorsal root ganglia (DRG), measured as axonal outgrowth.;VEGF was found to stimulate axonal outgrowth from DRG, both by an action on the growing axons and the nerve cell bodies.
VEGF (>10 ng/ml) stimulated 5-bromo-2a-deoxyuridine (BrdUrd) incorporation into cells that expressed immature neuronal marker proteins and increased cell number in cultures by 20–30%.;Here we report that VEGF(165) has neurotrophic actions on cultured adult mouse superior cervical ganglia (SCG) and dorsal root ganglia (DRG), measured as axonal outgrowth.;VEGF was found to stimulate axonal outgrowth from DRG, both by an action on the growing axons and the nerve cell bodies.
Our results show that the percentage of LDH released as a result of ER stress was significantly lower in astrocytes with an overexpression of CDNF than in the control groups without CDNF overexpression, indicating that CDNF alleviates ER stress-induced astrocyte damage. The secretion and mRNA expression levels of pro-inflammatory cytokines were increased by tunicamycin, and this stimulation was significantly suppressed by an overexpression of CDNF, demonstrating that CDNF plays an important role in astrocyte inflammation and functioning by resisting ER stress.
Compared to glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF), MANF was more selective in the protection of dopaminergic neurons at lower (0.05–0.25 ng/mL) and middle (0.5–2.5 ng/mL) concentrations: MANF>GDNF>BDNF.
Mouse neudesin mRNA was expressed in neurons but not glial cells of the brain. The protein exhibited significant neurotrophic activity in primary cultured mouse neurons but not mitogenic activity in primary cultured mouse astrocytes.;Neudesin significantly promoted neuronal differentiation and overrode the undifferentiated state of the neural precursor cells sustained by fibroblast growth factor 2 (FGF2).
Artemin is a survival factor for sensory and sympathetic neurons in culture, and its expression pattern suggests that it also influences these neurons in vivo. Artemin can also activate the GFRalpha1–RET complex and supports the survival of dopaminergic midbrain neurons in culture, indicating that like GDNF (GFRalpha1–RET) and NTN (GFRalpha2–RET), Artemin has a preferred receptor (GFRalpha3–RET) but that alternative receptor interactions also occur.
Here, we report that neurturin, like GDNF, increases the choline acetyltransferase activity of normal postnatal motor neurons, induces neurite outgrowth in spinal cord, and potently protects motor neurons from chronic glutamate-mediated degeneration.
Persephin, like GDNF and NTN, promotes the survival of ventral midbrain dopaminergic neurons in culture and prevents their degeneration after 6-hydroxydopamine treatment in vivo.
These data show that both SF/HGF and FGF-1 protect cerebellar granule neurons against excitotoxicity with similar potency in a PI3-K/Akt-dependent and MAP-kinase/CREB-independent manner.;Continuous postischemic intrastriatal administration of human recombinant HGF (10 or 30 µg) for 7 days potently prevented the delayed death of hippocampal neurons under both anesthetized and awake conditions.
Pre-incubation with VP22-ADNP enriched protein fractions protected against beta amyloid peptide toxicity and oxidative stress (H2O2) in PC12 cells. VP22 by itself was devoid of protective activity.
Meteorin selectively promoted astrocyte formation from mouse cerebrocortical neurospheres in differentiation culture, whereas it induced cerebellar astrocytes to become radial glia. Meteorin also induced axonal extension in small and intermediate neurons of sensory ganglia by activating nearby satellite glia.;Here, we show that METRN promotes migration of neuroblasts from SVZ explants of postnatal rats and stroke-subjected adult rats via a chemokinetic mechanism, and reduces N-methyl-D-asparate-induced apoptotic cell death in SVZ cells in vitro.;Here, we demonstrate that meteorin is involved in GFAP-positive glial differentiation through activation of the Jak-STAT3 pathway, by using neurosphere and retinal explant culture systems.
MK at the optimal concentration of 10 ng/ml promoted the survival of mouse mesencephalic neurons in culture as demonstrated by the increased number of microtubule-associated protein-2 (MAP2) immunostaining-positive and tyrosine hydroxylase immunostaining-positive neurons and an elevated uptake of radiolabeled dopamine.; To examine the neurite-guiding activity of MK, rat embryonic brain cells (embryonic days 17-18) were cultured on plates coated with purified MK in a grid pattern. The cells attached to and extended their neurites along the substrate pattern.
Using human neuroblastoma SH-SY5Y cells, we found that the neuroprotective function of CHRNA7 is blocked by CHRNA7 knockdown using RNA interference. [...] Furthermore, activation of CHRNA7 is neuroprotective both in vitro (Martin et al., 2004 Qi et al., 2007) and in vivo (Di Cesare Mannelli et al., 2014 Liu et al., 2012).;These findings indicate that alpha7 nAChR may play a significant neuroprotective role by enhancing cleavage of APP by alpha-secretase, regulating signal transduction, improving antioxidant defenses and inhibiting the toxicity of Abeta, which is connected with the pathogenesis of AD
We observed that this aberrant phenotype can be reversed by the expression of the cochaperone BAG1 (Bcl-2-associated athanogene 1), restoring DJ-1 subcellular distribution, dimer formation, and chaperone activity and ameliorating cell survival.; In summary, we present BAG1 as a therapeutic tool modulating key steps in htt toxicity in vitro and ameliorating htt toxicity in vivo.
The association of AQP4 and GLT-1 could greatly supplement previous research regarding neuroprotection against AD.;Currently, it has been suggested that AQP4 influences synaptic plasticity, and AQP4 deficiency may impair learning and memory, in part, through glutamate transporter-1 (GLT-1).
Using cultures derived from embryonic day 14.5 (E14. 5) rat ventral mesencephalon, we show that Shh is also trophic for dopaminergic neurons.
In conclusion, results suggest that DEX treatment reduces cerebral ischemia-induced oxidative stress, cell death, and intracellular Ca2+ signaling through inhibition of TRPM2 and TRPV1 in the rat hippocampus and DRG;Recent studies indicate that TRPM2, a member of the TRPM subfamily of Ca(2+)-permeant, non-selective cation channel, plays an important role in mediating cellular responses to a wide range of stimuli that, under certain situations, can induce cell death.
In complementary tissue culture experiments, recombinant human TTR suppressed the cytotoxicity of soluble Aß aggregates added to mouse neurons and differentiated human SH-SY5Y neuroblastoma cells.
TRH and its synthetic analogs have been recognized as trophic factors in neurons of the diencephalon and spinal cord, and as neuroprotectants against oxidative stress, glutamate toxicity, caspase-induced cell death, DNA fragmentation, and inflammation.
Supplementation of cells with exogenous calpastatin was able to reverse the toxic effect of METH on reduction in cell viability and tyrosine hydroxylase phosphorylation.;Ab-toxicity was attenuated in the high calpastatin-containing NDMh-infected cells, as shown by inhibition of calpain activation and activity, no membrane permeability, normal cell morphology, and maintenance of mitochondrial enzyme activity (similar to attenuation of Ab-toxicity in non-infected cells overexpressing calpastatin following calpastatin-plasmid introduction into the cells).
Taken together, our data indicate that NMNAT2 exerts its chaperone or enzymatic function in a context-dependent manner to maintain neuronal health.
Our data suggest that selective AT2R-stimulation improves functional recovery in experimental spinal cord injury through promotion of axonal plasticity and through neuroprotective and anti-apoptotic mechanisms.
Taken together, our results suggest VGF enhances dendritic maturation and that these effects can be altered by common mutations in the VGF gene.
Our results provide evidence that ADAM 10 has alpha-secretase activity and many properties expected for the proteolytic processing of APP. Increases of its expression and activity might be beneficial for the treatment of Alzheimer's disease.;The amyloid precursor protein (APP) undergoes constitutive shedding by a protease activity called a-secretase. This is considered an important mechanism preventing the generation of the Alzheimer’s disease amyloid-b peptide (Ab) [...] We conclude that ADAM10 is the physiologically relevant, constitutive alpha-secretase of APP.
Results suggest SIRT1 activators can mediate neuroprotective effects during optic neuritis by these mechanisms, and they have the potential to preserve neurons in other neurodegenerative diseases that involve oxidative stress.;These findings show a neuroprotective role for Sirt1 in mammalian Huntington’s disease models and open new avenues for the development of neuroprotective strategies in Huntington’s disease;These results indicate that SIRT1 activation by either RSV or overexpression of SIRT1 can exert neuroprotective effects partly by inhibiting p53 acetylation in NMDA-induced neurotoxicity.
Genetic inhibition of SIRT2 via small interfering RNA similarly rescued a-synuclein toxicity. Furthermore, the inhibitors protected against dopaminergic cell death both in vitro and in a Drosophila model of Parkinson's disease.;In summary, the current study demonstrated the neuroprotective effects of SIRT2 inhibition in ischemic stroke, and identified the downregulation of AKT/FOXO3a and MAPK pathways as intermediary mechanisms which may contribute to the reduction in apoptotic cell death by SIRT2 inhibition.; The Sirtuin-2 Inhibitor AK7 Is Neuroprotective in Models of Parkinson’s Disease but Not Amyotrophic Lateral Sclerosis and Cerebral Ischemia.
Using primary neuronal cultures from the cerebellum, cerebral cortex, and hippocampus, we demonstrate that CRH exerts a brain region-specific neuroprotective effect on amyloid beta 25–35 toxicity.
T-III was also able to efficiently remove the superoxide anion, which was generated from the xanthine/xanthine oxidase system. These results strongly suggest that MT-III is involved in the protection of reactive oxygen species-induced DNA damage, probably via direct interaction with reactive oxygen species, and that MT-III acts as a neuroprotective agent.;Furthermore, induction of MT synthesis with Zn and Cd can protect human CNS cells from radiation-induced cytocidal and sublethal injuries.;Among MTs, a brain-predominant subtype MT-III has prominent neuroprotective activity against various types of damage. Here we show that the expression of MT-III is induced in cultured normal human astrocytes by hypoxia, and that overexpressed MT-III protects human embryonic kidney cells from hypoxia, suggesting that MT-III can protect the brain from hypoxic damage.;Metallothionein-III (MT-III) protects cerebral cortical neurons in established culture from the toxic effect of amyloid ß peptides (Aßs).;MT-3 overexpression in these cells also significantly suppressed MPP+- and salsolinol-induced apoptosis.
Ex vivo studies showed that overexpression of CPE in cultured hippocampal neurons protected them against H(2)O(2) oxidative-stress induced cell death.;Reducing CPE by approximately 30% using shRNA also increased ER stress and apoptosis. Conversely, overexpression of CPE partially rescued beta-cells from palmitate-induced ER stress and apoptosis.;Overexpression of CPE in hippocampal neurons, or CRS in mice, resulted in elevated prosurvival BCL2 protein/mRNA and p-AKT levels in the hippocampus, however, CPE-/- mice showed a decrease. Thus, during mild CRS, CPE expression is up-regulated, possibly contributed by glucocorticoids, to mediate neuroprotection of the hippocampus by enhancing BCL2 expression through AKT signaling, and thereby maintaining allostasis.
On the contrary, Koga et al73 recently showed that overexpression of wild-type OPTN results in increased apoptosis of RGCs and that OPTN (wild type or the E50K mutant form), unlike MYOC, is devoid of effects on neurite outgrowth in neuronal cells.
We report here that another FGF family member, FGF-8 is able to protect rat hippocampal cultures from oxidative stress. The b isoform of FGF-8 protected hippocampal cultures from hydrogen peroxide with an EC50 of approximately 25 ng/ml.;Mesenchymal stromal cells were cultivated for 2 to 3 passages and neural differentiation was induced with fibroblast growth factor 2, fibroblast growth factor 8, and brain-derived neurotrophic factor.;Functionally, FGF8 promoted neurite outgrowth in human neuroblastoma SK-N-MC cells as well as in rat pheochromocytoma PC12 cells, suggesting that FGF8 acts as a neurotrophic factor. FGF8 also supported neuronal survival and differentiation in cultured human neural progenitor cells.
Herein we demonstrate that tissue inhibitor of matrix metalloproteinase-3 (TIMP3), a soluble protein released by MSCs, is neuroprotective and enhances neuronal survival and neurite outgrowth in vitro.
PTHrP mRNA was persistently expressed before and after the time of commitment of granule neurons to apoptosis when they are cultured in the presence of 25 mMKCl or both 150 uM N-methyl-D-aspartic acid and 15 mMKCl, both of which promote the survival of these neurons. [...]  The addition of anti-PTHrP antiserum to the culture medium resulted in a reduction of the activity-dependent survival of the granule neurons.;PTHrP-null embryonic mixed cerebral cortical cultures were more sensitive to kainic acid than control cultures, and PTHrP addition was found to be protective against kainate toxicity in both PTHrP-null and control cultures.
In the absence of MPP+, the treatment of FGF9-neutralizing antibody-induced DA neuronal apoptosis whereas FGF9 protein reduced it indicating that endogenous FGF9 is a survival factor for DA neurons. We conclude that MPP+ down-regulates FGF9 expression to cause DA neuron death and that the prevention of FGF9 down-regulation is involved in melatonin-provided neuroprotection.;Simultaneous treatment with FGF9 and MPP+ prevented MPP+-induced neuron death and H2O2 overproduction but did not affect the FGF9-increased a-GCS and HO-1 protein expression.[...] These results indicate that FGF9 upregulates a-GCS and HO-1 expression to protect cortical and dopaminergic neurons from MPP+-induced oxidative insult.;Expression of each FGFR and effects of the preferred ligand for FGFR-3, FGF9, upon RGC survival and neurite outgrowth were examined in primary retinal cell cultures: whereas there was no stimulation of neuritogenesis, RGC survival was promoted in a dose-dependent manner (ED50 500 pg/ml, mean maximal increase of 60%) and could be completely blocked by addition of FGF9 neutralising antibody.
Unlike growth hormone, central treatment with prolactin failed to rescue neurons in this paradigm. This was confirmed in vitro, rat prolactin failed to protect neurons under conditions for which growth hormone was neuroprotective. However, prolactin had trophic and pro-proliferative effects on glia (P<0.001).
Coimmunoprecipitation data demonstrated that overexpression of NLK protein reduced ß-catenin binding to LEF-1. Our results suggested that NLK was associated with neuronal apoptosis through attenuating the Wnt/ß-catenin signaling pathway after SCIs.;Activated NLK directly phosphorylates microtubule-associated protein-1B (MAP1B) and the focal adhesion adaptor protein, paxillin. Knockdown of NLK attenuates the phosphorylation of both paxillin and MAP1B and inhibits both the NGF-induced re-distribution of F-actin and neurite outgrowth.;NLK suppressed proliferation, induced apoptosis and mediated c-Myb degradation in MCF-7 cells via a mechanism that seems to involve c-myc and Bcl2.
CART peptide promotes the survival of hippocampal neurons by upregulating brain-derived neurotrophic factor
Progranulin functions as a neurotrophic factor to regulate neurite outgrowth and enhance neuronal survival […] PGRN/GRN is a neurotrophic factor with activities that may be involved in the development of the nervous system and in neurodegeneration […] The full-length precursor, PGRN, exerted similar neurotrophic properties, both in motor and cortical neurons (Fig. 2, E and F). The maximal effect observed was a 38.5 and 22.0% increase in neuronal survival for motor and cortical neurons, respectively. ;Extracellular progranulin protects cortical neurons from toxic insults by activating survival signaling. […] ERK1/2 and Akt signaling mediate the neuroprotective activities of PGRN against MPP+ toxicity;Progranulin promotes neurite outgrowth and neuronal differentiation by regulating GSK-3ß […] PGRN induces neurite outgrowth in primary cultures of mouse cortical neurons.
ALS2/Alsin Regulates Rac-PAK Signaling and Neurite Outgrowth [...] ALS2 promotes neurite outgrowth in cultured rat cortical neurons.;Alsin/Rac1 signaling controls survival and growth of spinal motoneurons.
The histone acetyltransferase p300 promotes intrinsic axonal regeneration […] p300 induces axonal regeneration and modifies the epigenome on select proregeneration promoters […] ;A Small Molecule Activator of p300/CBP Histone Acetyltransferase Promotes Survival and Neurite Growth in a Cellular Model of Parkinson’s Disease
TAT-mediated delivery of neuroglobin attenuates apoptosis induced by oxygen–glucose deprivation via the Jak2/Stat3 pathway in vitro […] Neuroglobin-mediated neuroprotection rescued cultured cells from OGD […] Our results demonstrate that TAT–Ngb can protect neuron-like cells against OGD-induced apoptosis by activating the Jak2/Stat3 pathway; Neuroprotective effects of neuroglobin after mechanical injury [...] Over-expressed NGB in injured B104 cells showed significant neuro- protective effects. Lactate dehydrogenase activity decreased and cell survival rates increased. Moderate and severe injuries had a higher NGB level than that in mild injury.
The neurotrophic effects of PACAP in PC12 cells: control by multiple transduction pathways;PACAP protects neuronal differentiated PC12 cells against the neurotoxicity induced by a mitochondrial complex I inhibitor, rotenone.;summarizes the findings on the neuroprotective potential of PACAP in models of neurodegenerative diseases, with special focus on in vitro and in vivo models of Parkinson`s disease, Huntington chorea and Alzheimer`s disease
Reduction of the neuroprotective transcription factor Npas4 results in increased neuronal necrosis, inflammation and brain lesion size following ischaemia […] Npas4, whose expression is robustly and transiently upregulated in the brain during the acute phase of ischaemia, plays a neuroprotective role because Npas4 deficiency increased the susceptibility of cultured neurons to cell death by OGD and exacerbated the severity of brain injury after photochemically-induced stroke in mice.;Reduced Npas4 expression during neural differentiation results in delayed neural differentiation
Neuroprotective effects of insulin against H2O2-induced oxidative stress in primary hippocampal cell culture […] Results shows that 12 and 24 hour after exposure to 50, 100 and 150 uM H2O2, significant neuronal damage and cell death was evident both in morphological and MTT analysis, while 0.5 uM insulin was not effective enough to prevent these damages, when primary hippocampal neurons were pretreated with 1 M insulin, neuronal damage induced by 50 and 100 uM H2O2 was prevented while this dose of insulin was not able to prevent neuronal damage induced by 150 uM H2O2.;The present study also indicates that insulin fails to stimulate glucose oxidation and glycogen syn- thase activity in neurons. On the other hand, insulin does promote the survival and differentiation of fetal chick neurons in culture. This trophic effect was observed at low concentrations of insulin (10 ng/ml) and was dependent on the continuous presence of insulin in the medium. The number of neurons surviving in the presence of insulin was fewer than the number in serum, suggesting that only a specific population of neurons is supported by insulin;Neuronal necrosis inhibition by insulin through protein kinase C activation.
Syt10 knock-out neurons are more susceptible to KA-induced cell death […] Syt10 is a neuroprotective downstream effector of NPAS4 in activity-induced neuronal cell death
Further analysis using realtime RT-PCR confirmed that we had identified genes that are regulated by single growth factors, as well as several more that are co-regulated by both IGF-1 and bFGF. These genes can influence neuronal survival by affecting diverse pathways such as growth factor signal transduction (CD44, DTR, DUSP6, EPS8, IGFBP3), DNA repair and transcription (FOXJ1), metabolic homeostasis (RASA1, SHMT2), cytoskeletal stability (MSN, MAPT) and cholesterol biosynthesis (FDFT1, FDPS).
In different cellular systems, TERT protein has been shown to be protective through its interaction with mitochondria. Our data reveal that TERT is expressed in vitro in mouse neurons and microglia, and in vivo in the cytoplasm of mature human hippocampal neurons and activated microglia, but is absent from astrocytes.;These data suggest that TERT plays a neuroprotective role via anti-apoptosis in neurons after OGD.;Our findings demonstrate a neuroprotective function of TERT in an experimental model  relevant  to  Alzheimer’s  disease, and  suggest  the  possibility  that  restoration  of  TERT expression  in  neurons  in  the  adult  brain  may  protect against  age-related  neurodegeneration.
Microscopic examination of glia suggested signs of toxicity in cultures treated with 100 uM oxyresveratrol, as demonstrated by elevated S-100B protein release and a high proportion of cells with condensed nuclei.;Using a well-characterized in vitro model of brain cell trauma, we have previously shown that strain injury causes S100B release from neonatal rat neuronal plus glial cultures and that exogenous S100B reduces delayed post-traumatic neuronal damage even when given at 6 or 24 h post-trauma. The purpose of the current studies was to measure post-traumatic S100B release by specific brain cell types and to examine the effect of an antibody to S100 on post-traumatic delayed (48 h) neuronal injury and the protective effect of exogenous S100B.;Our data suggest that selective activation of CB1 receptors by either exogenous or endogenous cannabinoids might afford neuroprotection in MPTP-induced neurotoxicity also by controlling S100B up-regulation in activated glial cells.;Our results have shown that at nanomolar concentrations, S100b protects cells against AP. mediated cytotoxicity and the protective mechanism could be related, almost in part, to the control of ROS production through an over expression of Myoglobin gene.
Fibroblast growth factor-20 protects against dopamine neuron loss in vitro and provides functional protection in the 6-hydroxydopamine-lesioned rat model of Parkinson's disease.
Prosaposin is an AR-target gene and its neurotrophic domain upregulates AR expression and activity in prostate stromal cells.
The data obtained indicate that the absence of PTN affects AKT pathway response and modulates the expression of genes related with neuroprotection (Mgst3 and Estrogen receptor 1, Ers 1) and cell differentiation (Caspase 6, Nestin, and Odz4), both in vivo and in vitro.
REPLACE
Here we report that Htt overexpression in other CNS-derived cells can protect them from more than 20 days exposure to fatal stimuli.[...] These data show that Htt inhibits neuronal cell death by interfering with the activity of the apoptosome complex.
Electroretinography, immunocytochemistry, quantitative histology, RT-PCR and Western blots were used to obtain data which showed that thioredoxin overexpression prevented loss of photoreceptors and retinal function. Analysis of signal pathways showed that thioredoxin up-regulated neurotrophic factors BDNF and GDNF and activated survival signaling pathways Akt, Ras/Raf1/ and the ERKs while inhibiting the ASK1/JNK apoptosis pathway.;In this study, we showed that Trx in the submicromolar range protects neuronal SH-SY5Y cells from apoptosis caused by serum deprivation or by MPP+. Using antisense oligonucleotides and reductase inhibitors, we showed that preconditioning treatment of SH-SY5Y cells with a non-lethal serum-free stress produces a hormesis effect mediated by the induction of Trx and leads to enhanced tolerance against oxidative stress and apoptosis induced by either serum deprivation or by MPP+.; Trx mRNA transcription was inhibited by H2O2 (300 µM), which could be reversed by the pre-administration of DHEA in various concentrations (0.1–100 nM). Western blot assay confirmed that protein level of Trx could be elevated by the pre-treatment of DHEA (10–100 nM) with the exposure of H2O2. Taken together, these data suggest that DHEA may be useful in treating age-related neurodegenerative diseases based on its up-regulating effects on an antioxidant and neuroprotective protein thioredoxin, a substrate in the Trx redox system.
NSE promoted the survival of neurons not only in neocortical cultures but also in mesencephalic and spinal cord cultures. Furthermore, NSE showed neuroprotective action on cultured neocortical neurons in a low-oxygen atmosphere.;We show that gamma-enolase-mediated PI3K activation regulates RhoA kinase, a key regulator of actin cytoskeleton organization. Moreover, the inhibition of RhoA downstream effector ROCK (Rho-associated kinase) results in enhanced gamma-enolase-induced neurite outgrowth, accompanied by actin polymerization and its redistribution to growth cones. Our results show that gamma-enolase controls neuronal survival, differentiation and neurite regeneration by activating the PI3K/Akt and MAPK/ERK signalling pathways, resulting in downstream regulation of the molecular and cellular processes of cytoskeleton reorganization and cell remodelling, activation of transcriptional factors and regulation of the cell cycle.; The upregulation of c-enolase in microglial cells in response to amyloid-b peptide (Ab) was confirmed in mouse microglial cell line EOC 13.31 and primary microglia and medium enriched with gamma-enolase proved to be neuroprotective against Ab toxicity, however, the effect was reversed by cathepsin X proteolytic activity. These results demonstrate an upregulation of gamma-enolase in microglia cells surrounding amyloid plaques in Tg2576 transgenic mice and demonstrate its neuroprotective role in amyloid-b-related neurodegeneration.
The purpose of this study was to evaluate the neuroprotective and axogenic properties of Nrn1 on axotomized retinal ganglion cells (RGCs) in vitro and on the in vivo optic nerve crush (ONC) mouse model. Axotomized cultured RGCs treated with recombinant hNRN1 significantly increased survival of RGCs by 21% (n=6–7, P<0.01) and neurite outgrowth in RGCs by 141% compared to controls (n=15, P<0.05). RGC transduction with AAV2-CAG–hNRN1 prior to ONC promoted RGC survival (450%, n=3–7, P<0.05) and significantly preserved RGC function by 70% until 28 days post crush (dpc) (n=6, P<0.05) compared with the control AAV2-CAG–green fluorescent protein transduction group.;We also showed that soluble recombinant neuritin, when chronically infused into the brains of Tg2576 mice, normalized synaptic plasticity in acute hippocampal slices, leading to intact long-term potentiation. By revealing the protective actions of soluble neuritin against AD-related neural defects, we provide a potential therapeutic approach for patients with AD.;Finally, the androgenic effect on neurite outgrowth was abolished by silencing neuritin with siRNA. Therefore, the trophic effects of androgens in motor neurones may be explained by the androgenic regulation of neuritin, a protein linked to neurone development, elongation and regeneration.;GRP78, caspase-12 and CHOP expression as well as apoptosis rate of primary cultured neurons and the ultrastructural changes of endoplasmic reticulum in the OGD/R + neuritin group significantly improved compared with the OGD/R group. In conclusion, the neuroprotection function of neuritin may be involved in ERS pathways.
GnRH was shown to induce changes in neurite outgrowth and length in rat cortical neurons in vitro.
In conclusion, Nurr1 overexpression exerts neuroprotective and anti-inflammatory roles via down-regulating CCL2 in both in vivo and in vitro PD models, contributing to developing mechanism-based and neuroprotective strategies against PD.;In the MPP(+)-pretreated PC12 cells, PPARgamma and Nurr1 agonists and their combined form resulted in a decrease in the cell death rate.
However, cells treated with exogenous extracellular DJ-1 during reperfusion exhibited significant rescue from OGD-induced cell death.
PC12 cells, when transfected with UCP2, were protected against free radical-induced cell death.
Functional modulation of THOP1 levels in primary cortical neurons demonstrated that its overexpression was neuroprotective against Abeta toxicity
Forced inhibition of ATF-3 expression using siRNA protects neurons against LK-induced apoptosis, whereas the over-expression of ATF-3 blocks GW5074-mediated neuroprotection.
We further found that both HDAC4 and HDAC5 increased cell viability through inhibition of HMGB1, a central mediator of tissue damage following acute injury, expression and release in PC12 cells.;We identified miR-22 as a potentially neuroprotective miRNA based on its predicted regulation of several targets implicated in Huntington's disease (histone deacetylase 4 (HDAC4), REST corepresor 1 (Rcor1) and regulator of G-protein signaling 2 (Rgs2)) and its diminished expression in Huntington's and Alzheimer's disease brains.
Using in vitro cultures of rat retinal explants exposed to NMDA, we found that NPY pretreatment prevented NMDA-induced cell death.;Using in vitro models of Alzheimer's disease (AD), we found that the toxic effects of amyloid beta 25-35 (Aß(25-35)) on the neurotrophin brain-derived neurotrophic factor (BDNF) were counteracted by pre-incubation with neuropeptide Y (NPY), a neuropeptide expressed within the central nervous system.;Thus, an increase of AMPA-receptor mediated neurodegeneration, in the mouse hippocampus, was prevented by neuroprotective pathways activated by NPY receptors (Y(1) and Y(2)), which can be affected by BDNF released by microglia and neurons.;The activation of Y(1) or Y(2) receptors 30min after starting the exposure to the excitotoxic insult with kainate resulted in neuroprotection by reducing the PI uptake in DG, CA1 and CA3 cell layers.
In an NSC34 cell line, glycosylation of GPNMB was inhibited by interaction with SOD1(G93A), increasing motor neuron vulnerability, whereas extracellular fragments of GPNMB secreted from activated astrocytes attenuated the neurotoxicity of SOD1(G93A) in neural cells.;These results demonstrate that GPNMB may exert its neuroprotective effect through reducing astrocyte-mediated neuroinflammation in a CD44-dependent manner, providing novel mechanistic insight into the neuroprotective properties of GPNMB.
Pharmacological augmentation of mitochondrial ROS increases Sirt3 expression in primary hippocampal culture with SIRT3 over-expression being neuroprotective.;Moreover, treatment with IC87201 and ZL006 significantly increased the expression of Sirt3 after MPP(+) exposure, and knockdown of Sirt3 using specific targeted small interfere RNA (siRNA) partially nullified the protective effects induced by these two inhibitors.;In conclusion, miR-494-3p inhibition exerted a neuroprotective role in MPP+-induced PD by targeting SIRT3, providing a possible therapeutic strategy for PD patients.;Furthermore, SIRT3 knockdown in NSCs via small interfering RNA (siRNA) accelerated cell injury, whereas SIRT3 overexpression provided resistance to microglia activation-induced oxidative stress cellular damage.
Early postnatal spiral ganglion cells (SGC) in a dissociated cell culture were used as a model of auditory innervation to test the trophic factors leukaemia inhibitory factor (LIF) and neurotrophin-3 (NT-3) for their ability, individually or in combination, to promote neuronal survival. The findings suggest that LIF supports neuronal survival in a concentration-dependent manner.
Using primary cultures of mouse cortical neurons, OsM was shown to reduce N-methyl-D-aspartate (NMDA) -induced neuronal death by 50% when added simultaneously with NMDA while pretreatment of neurons with OsM fully prevented NMDA toxicity indicating a profound protective effect of this cytokine. OsM was also shown to inhibit NMDA-mediated increase in levels of free intracellular calcium and to selectively reduce neuronal expression of the NR2C subunit of the NMDA receptor.;Furthermore, OSM dose-dependently promoted neurite outgrowth in cultured neurons, indicating that the cytokine plays an additional role in CNS repair.
When B35 neurons were subjected to oxygen glucose deprivation (OGD)/reoxygenation or glutamate, widespread neuronal death was seen after both treatments. Treatment with NRG-1 immediately after OGD significantly increased neuronal survival.;Moreover, NRG1 reduced the number of Swe-APP- and Aß(1-42)-induced TUNEL-positive SH-SY5Y cells and primary cortical neurons, respectively. NRG1 reduced the accumulation of reactive oxygen species and attenuated Swe-APP-induced mitochondrial membrane potential loss.
Here, we show that BMP7 treatment of rats subjected to mild cervical SCI significantly increased the pro-survival mitogen-activated protein kinase-38 (MAPK-38) pathway and levels of N-methyl-D-aspartate receptor 1 (NMDAR-1) resulting in a significant increase in neuronal sparing in the ventral horn of the spinal cord. Moreover, BMP7 was neuroprotective against glutamate-mediated excitotoxicity in cultured cortical neurons.;Subsequent in vitro analyses of E14.5 cortical cells revealed that lack of Bmp7 affects neural progenitor cells, evidenced by their reduced proliferation, survival and self-renewal capacity. Addition of BMP7 was able to rescue these proliferation and survival defects.
We found that neurons treated with IGF-II after CORT incubation showed reduced oxidative stress damage and recovered antioxidant status (normalized total antioxidant status, lipid hydroperoxides and NAD(P) H:quinone oxidoreductase activity). [...] IGF-II was also able to recover the long-lasting neuronal cell damage.;IGF1 receptor (IGF1R) immunoreactivity was predominantly expressed by neurons, and both IGF1 and IGF2 significantly protected neurons from cytokine (IL-1/IFNa) induced death.
Here we show that the leptin (116–130) fragment, but not leptin (22–56), mirrored the ability of leptin to promote AMPA receptor trafficking to synapses and facilitate activity-dependent hippocampal synaptic plasticity. Administration of leptin (116–130) also mirrored the cognitive enhancing effects of leptin as it enhanced performance in episodic-like memory tests. Moreover, leptin (116–130) prevented hippocampal synaptic disruption and neuronal cell death in models of amyloid toxicity.
In this study, we found that BMP2 exerts neurotrophic effects, including a neuroprotective effect against nocodazole-induced neuritic degeneration, on neuronal cells. We also found that BMP2-induced neurotrophic effects are directly involved in Smad-dependent signaling as well as PI3K/PTEN-Akt-mTOR signaling.
CNTF and BMP4, but not NGF or BDNF, greatly reduced the number of cells destroyed by toxin treatment indicating that these factors protect retinal neurons from a severe excitotoxic insult.;Interestingly, pharmacological inhibition of the ALK2 receptor prevented neuroprotection by STI1, while activation of ALK2 receptors by bone morphogenetic protein 4 (BMP4) either before or after OGD was effective in decreasing neuronal death induced by ischemia.
Application of H(2)O(2) increased lactate dehydrogenase activity and decreased the density of MAP-2(+) neurons in culture. Both responses were attenuated by BMP6 pretreatment.;Our data demonstrated that BMP6 prevented apoptosis induced by a high dose of Aß25-35, and inhibited rod formation induced by low dose of Aß25-35 in hippocampal neurons.;We demonstrate that presence of BMP6 either before or after H(2)O(2)-induced injury protects the cultured primary cortical cells from apoptosis.
In Neuro-2a neuroblastoma cells, expression of either EFA6A or SNX1 induced neurite outgrowth, which was further enhanced by co-expression of EFA6A and SNX1.
In Neuro-2a neuroblastoma cells, expression of either EFA6A [PSD] or SNX1 induced neurite outgrowth, which was further enhanced by co-expression of EFA6A and SNX1.
The neurotoxic effect of rotenone (25nM) on dopaminergic neurons is reversed by addition of PEDF. [..] PEDF (1ng/ml) has also a neuroprotective effect in the 6-OHDA midbrain in vitro model.
We found that activation of NTRK2 is able to confer a full growth phenotype of Ba/F3 cells in an IL3-independent manner in the PTEN-null setting.
CNTF and BMP4, but not NGF or BDNF, greatly reduced the number of cells destroyed by toxin treatment indicating that these factors protect retinal neurons from a severe excitotoxic insult.
FGF-2 increased the number of proliferating cells in the subventricular zone by 30% in wild-type mice, and by 150% in HD transgenic R6/2 mice. [...] FGF-2 was neuroprotective as well, because it blocked cell death induced by mutant expanded Htt in primary striatal cultures.;Thus, our results demonstrate for the first time that the FGF2/ATP complex but not FGF2 alone mediates neuroprotection.;In  addition, co-culture of dopaminergic neurons with high molecular weight fibroblast growth factor-2 over-expressing Schwann cells revealed an increased survival and neurite formation of the mesencephalic dopaminergic neurons. These results suggest that the high molecular weight fibroblast growth factor-2 isoforms may serve as a new tool for the treatment of Parkinson's disease.;These data strongly suggest that bFGF and BDNF promote the formation of neuronal circuits as well as survival and that optical recording of organotypic hippocampal slices would be a useful technique that enables us to analyze neuronal circuit formation easily.;Our study shows that stimulation of glial cells by bFGF allows the up-regulation of antioxidant defenses and supports cell survival during oxidative stress.
The addition of FGF-19 to Y79 retinoblastoma or primary adult pig photoreceptor cultures led to time- and dose-dependent changes in proliferation (for Y79) or survival (for primary photoreceptors). [...] The addition of FGF-19 led to the reexpression of Nrl immunoreactivity in both culture models.;These data indicate a physiological role for FGF-19 in adult photoreceptor phenotypic maintenance and survival and argue in favor of its use as a neuroprotectant.
The results showed that both migration and proliferation was induced by FGF8.
Exogenous FGF-21 protein completely protected aging neurons from glutamate challenge. This neuroprotection was associated with enhanced Akt-1 activation and GSK-3 inhibition.
Administration of FGF13 not only promoted neuronal polarization, axon formation, and growth cone initiation in vitro, but it also facilitated functional recovery following SCI. In addition, we found that upregulation of FGF13 in primary cortical neurons was accompanied by enhanced mitochondrial function, which is essential for axon regeneration.
An adenovirus expressing a constitutively active form of TGF-beta 1 was injected intracerebrally 1 week before the induction of excitotoxic lesion, and neuronal protection was observed. To confirm the neuroprotective role of TGF-beta 1, the TGF-beta 1 adenovirus was replaced by recombinant human TGF-beta 1 protein and total neuroprotection was observed.;In vitro, TGF-beta1 protects neurons against excitotoxicity by inhibiting the t-PA-potentiated NMDA-induced neuronal death through a mechanism involving the up-regulation of the type-1 plasminogen activator inhibitor (PAI-1) in astrocyte
Pretreatment of rat primary hippocampal neurons and mouse hippocampal neuronal cell line HT22 with recombinant Klotho protected these cells from glutamate and oligomeric amyloid ß (oAß)-induced cytotoxicity. In addition, primary hippocampal neurons obtained from Klotho-overexpressing mouse embryos were more resistant to both cytotoxic insults, glutamate and oAß, compared with neurons from wild-type littermates.;Here, we show that klotho is a key factor underlying the neuroprotective effect of latanoprost during post-axotomy retinal ganglion cell (RGC) degeneration.
We found that JAZ protects cerebellar granule neurons against potassium deprivation-induced death and cortical neurons from death resulting from oxidative stress. JAZ also protects neurons against toxicity induced by mutant huntingtin and mutant ataxin-1 expression.
CHL1-Fc saved the same number of motoneurons as did L1-Fc, whereas P0-Fc had little neurotrophic activity at the same concentrations. Survival induced by L1 and CHL1 was completely inhibited by 20 microM LY294002 and PD98059, indicating that both MEK and PI3K pathways are required for signaling by these molecules.
L1-Fc prevented the death of approximately half of the motoneurons that were saved by BDNF in a dose-dependent manner (EC50 = 10 pM). CHL1-Fc saved the same number of motoneurons as did L1-Fc, whereas P0-Fc had little neurotrophic activity at the same concentrations.
SCO-spondin stimulates neuronal differentiation and neurite growth in vitro. [...] The objective of this work was to assess the neuroprotective and neuroregenerative properties of NX210 in vitro and in vivo for the treatment of spinal cord injury (SCI). In vitro studies were carried out on the B104 neuroblastoma cell line demonstrating neuroprotection by the resistance to oxidative damage using hydrogen peroxide and the measure of cell viability by metabolic activity.
Our data suggests that moderate elevated brain Epo levels provide clinically significant neuroprotection in EAE without modulation of the immune response making a significant contribution.;The synergistic combination dose down regulated neuroinflammatory genes (Tnf-a, Il1b, Nf-kB, and iNos) and upregulated the neuroprotective genes (Bcl-2, Bcl-xl, Hif-1, and Epo).;The established EPO-overexpressing NIH/3T3 cell line, EPO-3T3-EGFP, may provide a material for future studies of cell-based therapies for neurodegenerative diseases via the secretion of EPO on a short-term, high-dose, regional basis.;These results imply that EPO might be a novel valuable agent for treating AGEs-induced Toxicity.
We show that Bok controls neuronal Ca(2+)homeostasis and bioenergetics and, contrary to previous assumptions, exerts neuroprotective activities in vitro and in vivo.
Our results indicate the potential therapeutic value of agonists selective for GAL1R in the prevention of neuronal cell death.
The obtained results showed that hypoxia/ischemia may trigger down-regulation of the brain AC-coupled PACAP/VIP receptors, with a consequent decrease of PACAP- and/or VIP-ergic-dependent cAMP-driven signaling. Moreover, our findings indicate that PACAP and VIP can prevent the deleterious effect of OGD on rat neuronal cells.