Regulation of Cell Survival by Secreted Proneurotrophins

Lee, Ramee; Kermani, Pouneh; Teng, Kenneth K.; Hempstead, Barbara L.

doi:10.1126/science.1065057

Cited by 1,487 publications

(1,361 citation statements)

References 23 publications

Supporting

Mentioning

1,289

Contrasting

Unclassified

Order By: Relevance

“…At involution, the action of pro-apoptotic molecules could be counterbalanced by the neurotrophins. Moreover, during this period, in sheep mammary glands, the concomitant expression of insulin-like growth factor binding protein 5 (IGFBP5) and the nuclear positivity of ERα (Colitti and Farinacci 2009;Colitti and Parillo 2013) has been also related to plasminogen activation (Stefanon et al 2002;Nǿrgaard et al 2008) or to matrix metalloproteinases (MMP9) (Khokha and Werb 2011) that regulated the cleavage of pro-neurotrophins to the mature form (Lee et al 2001;Cao et al 2014). It could be of interest to detect at involution the expression of p75-NTR that induces apoptosis when binds BDNF.…”

Section: Discussionmentioning

confidence: 99%

Expression of NGF, BDNF and their high-affinity receptors in ovine mammary glands during development and lactation

Colitti

2015

Histochem Cell Biol

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Expression of NGF, BDNF and their high-affinity receptors in ovine mammary glands during development and lactation

Colitti

2015

Histochem Cell Biol

View full text Add to dashboard Cite

“…Activation of the two receptor types can elicit opposing effects -survival and differentiation via Trks, or apoptosis via p75NTR 9,10 . Adding to the complexity, TrkA and TrkC can act as dependence receptors that elicit apoptosis when unstimulated 11 , and the biological effect of secreted proneurotrophins might depend on the expression ratio of Trk receptors and p75NTR 12,13 and on expression of p75NTR co-receptors 14,15 .…”

Section: Schwann Cells and Their Interactionsmentioning

confidence: 99%

Schwann cell interactions with axons and microvessels in diabetic neuropathy

et al. 2017

View full text Add to dashboard Cite

The incidence of diabetes mellitus has increased dramatically over the past two to three decades. According to the International Diabetes Federation Diabetes Atlas, 415 million people worldwide had diabetes in 2015, and this number is expected to grow by 5% annually, predominantly as a result of increasing prevalence of type 2 diabetes. Furthermore, an estimated 100 million Europeans and 80 million Americans have impaired glucose tolerance or prediabetes. Few people die from acute diabetes in countries with comprehensive health care systems, but the disease is inflicting a huge medical, social and economic burden on society owing to the need for lifelong treatment of its systemic consequences and the insidious development of multi-organ damage.Peripheral neuropathy (BOXES 1,2) is a common but often neglected complication of long-term diabetes, and the lack of treatment options reflects an incomplete understanding of the pathogenic mechanisms. Hyperglycaemia is generally accepted as the primary pathogenic insult in type 1 and type 2 diabetic neuropathy, although roles are emerging for other factors, such as impaired insulin signalling, hypertension and dyslipidaemia (particularly for type 2 diabetes), which might precede overt hyperglycaemia 1 . Many preclinical studies, and occasional clinical studies, have indicated that diabetic neuropathy -like diabetic nephropathy and retinopathy -results from microvascular disease, with a focus on axonal degeneration as a consequence of ischaemia and/or hypoxia. This mechanism, however, is likely to be only one aspect of a more complex pathogenesis.The earliest descriptions of pathology in diabetic neuropathy indicated that Schwannopathy accompanied axonal degeneration. The majority of clinical and basic research in diabetic neuropathy since then has focused on the effects on neurons. However, accumulating data from research into the development and regeneration of the PNS has identified Schwann cells as equally indispensable components that maintain neuronal structure and function, nourish axons, and promote survival and growth upon injury. The early reports from 1979 that demonstrated morphological changes in Schwann cells in human diabetic neuropathy 2 are now supported by an increased awareness of molecular alterations in Schwann cells during diabetes 3 . Schwann cells express a wide range of receptors and, when they sense insults or danger signals, they upregulate synthesis and secretion of factors that stimulate neuroprotection, regrowth and remyelination, or factors that aggravate disease phenotypes 4 . The most recent studies have demonstrated that Schwann cells regulate many aspects of axonal function, so that disruption of their metabolism by diabetes results in the accumulation of neurotoxic intermediates and compromises production of neuronal support factors, contributing to axonal degeneration, endothelial dysfunction and diabetic neuropathy. Abstract | The prevalence of diabetes worldwide is at pandemic levels, with the number of patients increasing by 5% annu...

show abstract

“…However, it is important to note that recent evidence shows that NGF exists normally as multiple isoforms in various tissues , and that some NGF isoforms promote sympathetic degeneration rather than survival and sprouting (Lee, et al, 2001). Therefore, it is critical to confirm that peri-infarct NGF promotes sympathetic neuritogenesis.…”

Section: Ngf Is Obligatory For Enhanced Sympathetic Sprouting By Perimentioning

confidence: 99%

Sympathetic hyperinnervation and inflammatory cell NGF synthesis following myocardial infarction in rats

et al. 2006

View full text Add to dashboard Cite

Sympathetic hyperinnervation occurs in human ventricular tissue after myocardial infarction and may contribute to arrhythmias. Aberrant sympathetic sprouting is associated with elevated nerve growth factor (NGF) in many contexts, including ventricular hyperinnervation. However, it is unclear whether cardiomyocytes or other cell types are responsible for increased NGF synthesis. In this study, left coronary arteries were ligated and ventricular tissue examined in rats 1-28 days post-infarction. Infarct and peri-infarct tissue was essentially devoid of sensory and parasympathetic nerves at all time points. However, areas of increased sympathetic nerve density were observed in the peri-infarct zone between post-ligation days 4-14. Hyperinnervation occurred in regions containing accumulations of macrophages and myofibroblasts. To assess whether these inflammatory cells synthesize NGF, sections were processed for NGF in situ hybridization and immunohistochemistry. Both macrophage1 antigen-positive macrophages and α-smooth muscle actin immunoreactive myofibroblasts expressed NGF in areas where they were closely proximate to sympathetic nerves. To investigate whether NGF produced by peri-infarct cells induces sympathetic outgrowth, we cocultured adult sympathetic ganglia with peri-infarct explants. Neurite outgrowth from sympathetic ganglia was significantly greater at post-ligation days 7-14 as compared to control tissue. Addition of an NGF function-blocking antibody prevented the increased neurite outgrowth induced by periinfarct tissue. These findings provide evidence that inflammatory cell NGF synthesis plays a causal role in sympathetic hyperinnervation following myocardial infarction.

show abstract

Regulation of Cell Survival by Secreted Proneurotrophins

Cited by 1,487 publications

References 23 publications

Expression of NGF, BDNF and their high-affinity receptors in ovine mammary glands during development and lactation

Expression of NGF, BDNF and their high-affinity receptors in ovine mammary glands during development and lactation

Schwann cell interactions with axons and microvessels in diabetic neuropathy

Sympathetic hyperinnervation and inflammatory cell NGF synthesis following myocardial infarction in rats

Contact Info

Product

Resources

About