Axon injury induced endoplasmic reticulum stress and neurodegeneration
Yang Hu
摘要：Injury to central nervous system axons is a common early characteristic of neurodegenerative diseases. Depending on its location and the type of neuron, axon injury otfen leads to axon degeneration, retrograde neuronal cell death and progressive permanent loss of vital neuronal functions. Although these sequential events are clearly connected, ample evidence indicates that neuronal soma and axon degenerations are active autonomous processes with distinct molecular mechanisms. By exploiting the anatomical and techni-cal advantages of the retinal ganglion cell (RGC)/optic nerve (ON) system, we demonstrated that inhibition of the PERK-eIF2α-CHOP pathway and activation of the X-box binding protein 1 pathway synergistically protect RGC soma and axon, and preserve visual function, in both acute ON traumatic injury and chronic glaucomatous neuropathy. The autonomous endoplasmic reticulum (ER) stress pathway in neurons has been implicated in several other neurodegenerative diseases. In addition to the emerging role of ER mor-phology in axon maintenance, we propose that ER stress is a common upstream signal for disturbances in axon integrity, and that it leads to a retrograde signal that can subsequently induce neuronal soma death. hTerefore manipulation of the ER stress pathway may be a key step toward developing the effective neuro-protectants that are greatly needed in the clinic.
机标关键词：neurodegenerative diseasescentral nervous systemendoplasmic reticulummolecular mechanismsER stressvisual functionbinding proteincell death
资助基金：grants from National Eye Institute(R01EY023295)grants from National Eye Institute( R01EY024932)BrightFocus Foundation(G2013046)National Multiple Sclerosis Society (RG 5021A1)
论文发表日期：2016-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：3( 1557-1559 )
英文信息