ProNGF Induces PTEN via p75<sup>NTR</sup>to Suppress Trk-Mediated Survival Signaling in Brain Neurons

Song, Wenyu; Volosin, Márta; Cragnolini, Andrea B.; Hempstead, Barbara L.; Friedman, Wilma J.

doi:10.1523/jneurosci.2581-10.2010

Cited by 91 publications

(69 citation statements)

References 56 publications

(79 reference statements)

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“…In vitro, motor neuron death was induced through activation of p75 NTR by either NGF or proNGF in the presence of BDNF survival signaling, consistent with previous reports that survival or death is regulated by the strength of competing signaling pathways (Song et al, 2010). However, NGF-induced cell death ensued even in the absence of Trk activity, i.e.…”

Section: Discussionsupporting

confidence: 89%

Inhibition of motor neuron death in vitro and in vivo by a p75 neurotrophin receptor intracellular domain fragment

Matusica

Alfonsi

Turner

et al. 2016

Journal of Cell Science

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The p75 neurotrophin receptor ( p75 NTR ; also known as NGFR) can mediate neuronal apoptosis in disease or following trauma, and facilitate survival through interactions with Trk receptors. Here we tested the ability of a p75NTR -derived trophic cell-permeable peptide, c29, to inhibit p75 NTR -mediated motor neuron death. Acute c29 application to axotomized motor neuron axons decreased cell death, and systemic c29 treatment of SOD1 G93A mice, a common model of amyotrophic lateral sclerosis, resulted in increased spinal motor neuron survival mid-disease as well as delayed disease onset. Coincident with this, c29 treatment of these mice reduced the production of p75 NTR cleavage products. Although c29 treatment inhibited mature-and pro-nerve-growth-factor-induced death of cultured motor neurons, and these ligands induced the cleavage of p75 NTR in motor-neuron-like NSC-34 cells, there was no direct effect of c29 on p75 NTR cleavage. Rather, c29 promoted motor neuron survival in vitro by enhancing the activation of TrkB-dependent signaling pathways, provided that low levels of brain-derived neurotrophic factor (BDNF) were present, an effect that was replicated in vivo in SOD1 G93A mice. We conclude that the c29 peptide facilitates BDNF-dependent survival of motor neurons in vitro and in vivo.

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Section: Discussionsupporting

confidence: 89%

Inhibition of motor neuron death in vitro and in vivo by a p75 neurotrophin receptor intracellular domain fragment

Matusica

Alfonsi

Turner

et al. 2016

Journal of Cell Science

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“…Although the increased Trk phosphorylation may imply a compensatory mechanism following a substantial decrease in total protein level, we did not observe a concurrent increase in downstream signaling molecules such as pAkt or PKC in this structure, which is normally associated with neuronal survival and plasticity. That the phosphorylated (activated) Trk receptor does not suppress the ability of proNGF to elicit caspase cleavage and apoptosis via p75NTR was demonstrated in vitro (Song et al 2010). Yet, once the downstream Akt pathway is activated, neurons attain increased resistance to proNGF-induced cell death, indicating that Trk and p75NTR signaling pathways interact downstream of the receptors but upstream of Akt.…”

Section: Discussionmentioning

confidence: 99%

BDNF transcripts, proBDNF and proNGF, in the cortex and hippocampus throughout the life span of the rat

Perović

Tešić

Djordjevic

et al. 2012

AGE

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Neurotrophins are established molecular mediators of neuronal plasticity in the adult brain. We analyzed the impact of aging on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) protein isoforms, their receptors, and on the expression patterns of multiple 5′ exon-specific BDNF transcripts in the rat cortex and hippocampus throughout the life span of the rat (6, 12, 18, and 24 months of age). ProNGF was increased during aging in both structures. Mature NGF gradually decreased in the cortex, and, in 24-month-old animals, it was 30 % lower than that in adult 6-month-old rats. The BDNF expression did not change during aging, while proBDNF accumulated in the hippocampus of aged rats. Hippocampal total BDNF mRNA was lower in 12-month-old animals, mostly as a result of a decrease of BDNF transcripts 1 and 2. In contrast to the regionspecific regulation of specific exon-containing BDNF mRNAs in adult animals, the same BDNF RNA isoforms (containing exons III, IV, or VI) were present in both brain structures of aged animals. Deficits in neurotrophin signaling were supported by the observed decrease in Trk receptor expression which was accompanied by lower levels of the two main downstream effector kinases, pAkt and protein kinase C. The proteolytic processing of p75NTR observed in 12-monthold rats points to an additional regulatory mechanism in early aging. The changes described herein could contribute to reduced brain plasticity underlying the age-dependent decline in cognitive function.

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“…It has been related that increase proNGF levels induce apoptosis in various types of cells under seizures and spinal cord injury [60,61]. Moreover, evidence indicate that pro-NGF inhibit the proliferation and differentiation of hippocampal neural stem or progenitor cells from postnatal mice [62].…”

Section: Ngf and Agingmentioning

confidence: 99%

The involvement of BDNF, NGF and GDNF in aging and Alzheimer's disease

Budni¹,

Bellettini-Santos²,

Mina³

et al. 2015

Aging and disease

332

188

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Aging is a normal physiological process accompanied by cognitive decline. This aging process has been the primary risk factor for development of aging-related diseases such as Alzheimer's disease (AD). Cognitive deficit is related to alterations of neurotrophic factors level such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and glial cellderived neurotrophic factor (GDNF). These strong relationship between aging and AD is important to investigate the time which they overlap, as well as, the pathophysiological mechanism in each event. Considering that aging and AD are related to cognitive impairment, here we discuss the involving these neurotrophic factors in the aging process and AD.

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ProNGF Induces PTEN via p75^NTRto Suppress Trk-Mediated Survival Signaling in Brain Neurons

Cited by 91 publications

References 56 publications

Inhibition of motor neuron death in vitro and in vivo by a p75 neurotrophin receptor intracellular domain fragment

Inhibition of motor neuron death in vitro and in vivo by a p75 neurotrophin receptor intracellular domain fragment

BDNF transcripts, proBDNF and proNGF, in the cortex and hippocampus throughout the life span of the rat

The involvement of BDNF, NGF and GDNF in aging and Alzheimer's disease

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ProNGF Induces PTEN via p75NTRto Suppress Trk-Mediated Survival Signaling in Brain Neurons

Cited by 91 publications

References 56 publications

Inhibition of motor neuron death in vitro and in vivo by a p75 neurotrophin receptor intracellular domain fragment

Inhibition of motor neuron death in vitro and in vivo by a p75 neurotrophin receptor intracellular domain fragment

BDNF transcripts, proBDNF and proNGF, in the cortex and hippocampus throughout the life span of the rat

The involvement of BDNF, NGF and GDNF in aging and Alzheimer's disease

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ProNGF Induces PTEN via p75^NTRto Suppress Trk-Mediated Survival Signaling in Brain Neurons