p75NTR and Sortilin Increase After Facial Nerve Injury

Provenzano, Matthew J.; Xu, Ningyong; Meer, Mark R. Ver; Clark, J. Jason; Hansen, Marlan R.

doi:10.1097/mlg.0b013e31814b8d9f

Cited by 31 publications

(28 citation statements)

References 23 publications

(40 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All three components were expressed in DRG and a portion of DRG neurons coexpressed sortilin and p75NTR. Following peripheral nerve transection, most of p75NTR-sortilin coexpressing neurons died after nerve transection [43,44]. The increased levels of sortilin and p75NTR expression along with massive neuronal degeneration in the substantia nigra of rats subjected to KA lesion were also observed in our previous study [7].…”

Section: P75ntr Acts As "Molecular Switch" For Commitment To Cell Deamentioning

confidence: 58%

The proNGF-p75NTR-Sortilin Signalling Complex as New Target for the Therapeutic Treatment of Parkinsons Disease

Chen

Yung²,

Chan³

et al. 2008

CNSNDDT

View full text Add to dashboard Cite

Growing evidence has shown that the p75 neurotrophin receptor (p75NTR) may play important roles in controlling neuronal survival or cell apoptosis within the central nervous system in development, and in pathological or neural injury. Recent studies have further revealed that p75NTR acts as a "molecular signal switch" that determines cell death or survival by three processes. First, pro-nerve growth factor (proNGF) triggers cell apoptosis by its high affinity binding to p75NTR, while NGF induces neuronal survival with low-affinity binding. Second, p75NTR mediates cell death by combining with co-receptor sortilin, whereas it promotes neuronal survival through combination with proNGF. Third, release of the intracellular domain chopper or cleavaged "short p75NTR" can independently initiate neuronal apoptosis. We have identified the cell self-destructive proNGF-p75NTR-sortilin signalling apparatus assembled in ventral tier dopamine neurons of the substantia nigra pars compacta, suggesting that p75NTR signalling might be involved in selective cell death mechanisms of substantia nigra neurons or disease progression of Parkinson's disease (PD). In addition, experimental manipulation of p75NTR benefited cell survival of cholinergic or motor neurons and improved disease progression of the neurodegenerative diseases Alzheimer's disease and Amyotrophic lateral sclerosis. The proNGF-p75NTR-sortilin signalling complex may thus provide new target for neuroprotection of substantia nigra neurons and the therapeutic treatment of PD.

show abstract

Section: P75ntr Acts As "Molecular Switch" For Commitment To Cell Deamentioning

confidence: 58%

The proNGF-p75NTR-Sortilin Signalling Complex as New Target for the Therapeutic Treatment of Parkinsons Disease

Chen

Yung²,

Chan³

et al. 2008

CNSNDDT

View full text Add to dashboard Cite

show abstract

“…These findings are consistent with recent reports showing increased immunolabeling for p75 NGFR in non-myelinating and supernumerary Schwann cells in three CMT1 mouse models (Guenard et al, 1996; Klein et al, 2014). The effects of p75 NGFR on Schwann cells after injury are complex as p75 NGFR has roles in both Schwann cell apoptosis (Syroid et al, 2000) and myelination, depending on ligand presentation and intracellular binding partners (Cosgaya et al, 2002; Provenzano et al, 2008; Teng et al, 2005; Tep et al, 2012). Signaling through p75 NGFR can lead to activation of c-Jun-dependent downstream signaling pathways to regulate Schwann cell survival and differentiation (Lindwall Blom et al, 2014; Shin et al, 2013; Yeiser et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling studies in regenerating nerves in a mouse model for CMT1X: Uninjured Cx32-knockout peripheral nerves display expression profile of injured wild type nerves

Freidin

Asche-Godin

Abrams

2015

Experimental Neurology

View full text Add to dashboard Cite

X-linked Charcot–Marie–Tooth disease (CMT1X) is an inherited peripheral neuropathy caused by mutations in GJB1, the human gene for Connexin32 (Cx32). This present study uses Ilumina Ref8-v2 BeadArray to examine the expression profiles of injured and uninjured sciatic nerves at 5, 7, and 14 days post-crush injury (dpi) from Wild Type (WT) and Cx32-knockout (Cx32KO) mice to identify the genes and signaling pathways that are dysregulated in the absence of Schwann cell Cx32. Given the assumption that loss of Schwann cell Cx32 disrupts the regeneration and maintenance of myelinated nerve leading to a demyelinating neuropathy in CMT1X, we initially hypothesized that nerve crush injury would result in significant increases in differential gene expression in Cx32KO mice relative to WT nerves. However, microarray analysis revealed a striking collapse in the number of differentially expressed genes at 5 and 7 dpi in Cx32KO nerves relative to WT, while uninjured and 14dpi time points showed large numbers of differentially regulated genes. Further comparisons within each genotype showed limited changes in Cx32KO gene expression following crush injury when compared to uninjured Cx32KO nerves. By contrast, WT nerves exhibited robust changes in gene expression at 5 and 7dpi with no significant differences in gene expression by 14dpi relative to uninjured WT nerve samples. Taken together, these data suggest the gene expression profile in uninjured Cx32KO sciatic nerve strongly resembles that of a WT nerve following injury and that loss of Schwann cell Cx32 leads to a basal state of gene expression similar to that of an injured WT nerve. These findings support a role for Cx32 in non-myelinating and regenerating populations of Schwann cells in normal axonal maintenance in re-myelination, and regeneration of peripheral nerve following injury. Disruption of Schwann cell-axonal communication in CMT1X may cause dysregulation of signaling pathways that are essential for the maintenance of intact myelinated peripheral nerves and to establish the necessary conditions for successful regeneration and remyelination following nerve injury.

show abstract

“…In addition to neurons, injury-induced increases in p75 NTR expression may occur in Schwann cells (Taniuchi et al, 1986;Gschwendtner et al, 2003;Zhou and Li, 2007;Provenzano et al, 2008), astrocytes (Choi and Friedman, 2009), oligodendrocytes (Beattie et al, 2002) or microglia/macrophages (Dowling et al, 1999;Wong et al, 2010). Why does expression of the p75 NTR increase in response to damage?…”

Section: Introductionmentioning

confidence: 95%

The p75 neurotrophin receptor: at the crossroad of neural repair and death

2015

View full text Add to dashboard Cite

The strong repair and pro-survival functions of neurotrophins at their primary receptors, TrkA, TrkB and TrkC, have made them attractive candidates for treatment of nervous system injury and disease. However, difficulties with the clinical implementation of neurotrophin therapies have prompted the search for treatments that are stable, easier to deliver and allow more precise regulation of neurotrophin actions. Recently, the p75 neurotrophin receptor (p75NTR) has emerged as a potential target for pharmacological control of neurotrophin activity, supported in part by studies demonstrating 1) regulation of neural plasticity in the mature nervous system, 2) promotion of adult neurogenesis and 3) increased expression in neurons, macrophages, microglia, astrocytes and/or Schwann cells in response to injury and neurodegenerative diseases. Although the receptor has no intrinsic catalytic activity it interacts with and modulates the function of TrkA, TrkB, and TrkC, as well as sortilin and the Nogo receptor. This provides substantial cellular and molecular diversity for regulation of neuron survival, neurogenesis, immune responses and processes that support neural function. Upregulation of the p75NTR under pathological conditions places the receptor in a key position to control numerous processes necessary for nervous system recovery. Support for this possibility has come from recent studies showing that small, non-peptide p75NTR ligands can selectively modify pro-survival and repair functions. While a great deal remains to be discovered about the wide ranging functions of the p75NTR, studies summarized in this review highlight the immense potential for development of novel neuroprotective and neurorestorative therapies.

show abstract

p75NTR and Sortilin Increase After Facial Nerve Injury

Abstract: FN axotomy increases p75 and sortilin expression in SCs, which correlates with increased apoptosis. These findings suggest roles for p75 and sortilin in SC loss after FN injury. Sortilin is a novel target in promoting FN healing after injury.

Cited by 31 publications

References 23 publications

The proNGF-p75NTR-Sortilin Signalling Complex as New Target for the Therapeutic Treatment of Parkinsons Disease

The proNGF-p75NTR-Sortilin Signalling Complex as New Target for the Therapeutic Treatment of Parkinsons Disease

Gene expression profiling studies in regenerating nerves in a mouse model for CMT1X: Uninjured Cx32-knockout peripheral nerves display expression profile of injured wild type nerves

The p75 neurotrophin receptor: at the crossroad of neural repair and death

Contact Info

Product

Resources

About