Nerve Growth Factor Signaling, Neuroprotection, and Neural Repair

Abstract

Nerve growth factor (NGF) was discovered 50 years ago as a molecule that promoted the survival and differentiation of sensory and sympathetic neurons. Its roles in neural development have been characterized extensively, but recent findings point to an unexpected diversity of NGF actions and indicate that developmental effects are only one aspect of the biology of NGF. This article considers expanded roles for NGF that are associated with the dynamically regulated production of NGF and its receptors that begins in development, extends throughout adult life and aging, and involves a surprising variety of neurons, glia, and nonneural cells. Particular attention is given to a growing body of evidence that suggests that among other roles, endogenous NGF signaling subserves neuroprotective and repair functions. The analysis points to many interesting unanswered questions and to the potential for continuing research on NGF to substantially enhance our understanding of the mechanisms and treatment of neurological disorders.

Direct isolation and RNA-seq reveal environment-dependent properties of engrafted neural stem/progenitor cells

“…Of the secreted neurohumoral substances, PDGF, IGF, TGF-β1 and IL-10 have critical roles in preventing neural apoptosis via the PI3K-Akt/NF-κB pathway [20][21][22]37 . Nerve growth factor and BDNF prevent activation of the mitochondrial apoptotic pathway via the P75NTR-mediated NF-κB pathway 23,38 . NF-κB activation induces the upregulation of anti-apoptotic genes, including Bcl-2 and Bcl-xL 20,23, and the Akt pathway could independently block the mitochondrial apoptotic pathway 23 .…”

“…Nerve growth factor and BDNF prevent activation of the mitochondrial apoptotic pathway via the P75NTR-mediated NF-κB pathway 23,38 . NF-κB activation induces the upregulation of anti-apoptotic genes, including Bcl-2 and Bcl-xL 20,23, and the Akt pathway could independently block the mitochondrial apoptotic pathway 23 . We demonstrated the activation of these mitochondrial apoptotic cascades following SCI to be attenuated by NSPC transplantation, providing a reasonable neuroprotective mechanism due to several neurohumoral factors.…”

“…Furthermore, we observed the activation of Akt and NF-κB (p65) (Fig. 2h), and a significant upregulation of their downstream transcriptional targets, Bcl-2 and Bcl-xL 20,23 (Fig. 2i), at 7 DAT in the NSPC-transplanted group, resulting in decreased activation of caspases 9 and 3 ( Fig.…”

“…Because these neurohumoral factors prevent neural apoptosis by the activation of the PI3K-Akt/NF-κB signalling pathway in vitro [20][21][22][23] , the neuroprotective effects through NSPC transplantation were examined. Histopathological examinations at 7 DAT revealed fewer TUNEL-positive cells and more spared myelin in the NSPC-transplanted group (Fig.…”

Human adipose tissue‐derived mesenchymal stem cells improve cognitive function and physical activity in ageing mice

“…Young BDNF 2/2 mice have reduced cholinergic innervation (Ward and Hagg, 2000) and a reduced number of cholinergic cells in the medial septum, which is accompanied by a decrease in ChAT activity in the hippocampus (Grosse et al, 2005). In contrast, BDNF and NGF promote survival of developing cholinergic forebrain neurons and attenuate the loss of neurons following excitotoxic insults (Burke et al, 1994;Sofroniew et al, 2001). In addition, NGF upregulates several cholinergic markers (Pongrac and Rylett, 1998;Oosawa et al, 1999;Auld et al, 2001), and BDNF is required for maturation of cholinergic nerves and plays a critical role in longterm potentiation required for memory consolidation (Ward and Hagg, 2000;Diogenes et al, 2011).…”