Retrograde apoptotic signaling by the p75 neurotrophin receptor

  • Pathak A
  • Carter B
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Abstract

Neurotrophins are target-derived factors necessary for mammalian nervous system development and maintenance. They are typically produced by neuronal target tissues and interact with their receptors at axonal endings. Therefore, locally generated neurotrophin signals must be conveyed from the axon back to the cell soma. Retrograde survival signaling by neurotrophin binding to Trk receptors has been extensively studied. However, neurotrophins also bind to the p75 receptor, which can induce apoptosis in a variety of contexts. Selective activation of p75 at distal axon ends has been shown to generate a retrograde apoptotic signal, although the mechanisms involved are poorly understood. The present review summarizes the available evidence for retrograde proapoptotic signaling in general and the role of the p75 receptor in particular, with discussion of unanswered questions in the field. In-depth knowledge of the mechanisms of retrograde apoptotic signaling is essential for understanding the etiology of neurodegeneration in many diseases and injuries. * ALS, : amyotrophic lateral sclerosis; BDNF, : brain-derived neurotrophic factor; DD, : death domain; DLK, : dual leucine zipper kinase; ECD, : extracellular domain; ERK, : extracellular signal-related kinase; GSK3, : glycogen synthase kinase 3β; ICD, : intracellular domain; ION, : isthmo-optic nucleus; JIP3, : JNK-interacting protein 3; JNK, : c-Jun N-terminal kinase; MAP, : mitogen-activated protein; MVB, : multivesicular body; NGF, : nerve growth factor; NRIF, : NTR-interacting factor; NT, : neurotrophin; NTR, : NT receptor; TACE, : TNFα-converting enzyme; SOD, : superoxide dismutase; TNF, : tumor necrosis factor; TRAF, : TNFR-associated factor

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APA

Pathak, A., & Carter, B. D. (2017). Retrograde apoptotic signaling by the p75 neurotrophin receptor. Neuronal Signaling, 1(1), NS20160007. https://doi.org/10.1042/ns20160007

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