Neuroprotection by eIF2 alpha-CHOP inhibition and XBP-1 activation in EAE/optic neuritiss

作者：Huang Haoliang; Miao Linqing; Liang Feisi; Liu Xiaodong; Xu Lin; Teng Xiuyin; Wang Qizhao; Ridder William H III; Shindler Kenneth S; Sun Yang; Hu Yang^*

来源：Cell Death & Disease, 2017, 8(7): e2936.

DOI：10.1038/cddis.2017.329

No therapies exist to prevent neuronal deficits in multiple sclerosis ( MS), because the molecular mechanism responsible for the progressive neurodegeneration is unknown. We previously showed that axon injury-induced neuronal endoplasmic reticulum (ER) stress plays an important role in retinal ganglion cell (RGC) death and optic nerve degeneration in traumatic and glaucomatous optic neuropathies. Optic neuritis, one of the most common clinical manifestations of MS, is readily modeled by experimental autoimmune encephalomyelitis (EAE) in mouse. Using this in vivo model, we now show that ER stress is induced early in EAE and that modulation of ER stress by inhibition of eIF2 alpha-CHOP and activation of XBP-1 in RGC specifically, protects RGC somata and axons and preserves visual function. This finding adds to the evidence that ER stress is a general upstream mechanism for neurodegeneration and suggests that targeting ER stress molecules is a promising therapeutic strategy for neuroprotection in MS.

• 出版日期2017-7