Speedy/RINGO: a molecular savior in spinal cord injury-based neurodegeneration?  

作　　者：Yesim Kaya Aysegul Yildiz 

机构地区：[1]Department of Molecular Biology and Genetics,Faculty of Science,Mugla Sitki Kocman University,Kotekli,Mentese,Mugla 48000,Turkey

出　　处：《Neuroimmunology and Neuroinflammation》2019年第3期6-20,共15页神经免疫与神经炎症（英文版）

基　　金：grants to Ayşegül Yıldız from Mugla Sitki Kocman University Scientific Research Project Office,Research and Development Projects(17/023);Arzu Karabay from The Turkish Academy of Sciences Distinguished Young Scientist Award(TÜBA-GEBIP);The Scientific and Technological Research Council of Turkey(TÜBİTAK);The Basic Sciences Research Group(TBAG)(108T811).

摘　　要：Endogenous or exogenous insults can cause spinal cord injury(SCI),often resulting in the loss of motor,autonomic,sensory and reflex functions.The pathogenesis of SCI comprises two stages.The primary injury stage occurs at the moment of trauma and is characterized by hemorrhage and rapid cell death.The secondary injury stage occurs due to progression of primary damage and is characterized by tissue loss and functional disorder.One of the most important cellular mechanisms underlying secondary injury is glutamate excitotoxicity,which overactivates the calpain protease via excessive Ca2+influx and induces neuronal apoptosis via p53 induction.Furthermore,Ca2+influx elicits apoptosis by inducing p53,thus negatively affecting two pathways:the mitogenic extracellular signal-regulated kinase/mitogenactivated protein kinase(ERK/MAPK)pathway and the survival phosphoinositide 3-kinase/protein kinase B(PI3K/AKT)pathway.Speedy/rapid inducer of G2/M progression in oocytes(Speedy/RINGO)is a cell cycle regulatory protein that increases survival of p53-positive mitotic cells by inhibiting the apoptotic machinery.Moreover,this protein elicits p53-dependent anti-apoptotic effects on calpain-induced degeneration of primary hippocampal neurons,amyotrophic lateral sclerosis motor neurons,and astrocytes and microglia in spinal cord lesions.The pathophysiology of SCI has not been fully elucidated and this hinders the development of powerful therapeutic strategies.This review focuses on the cellular mechanisms underlying the anti-apoptotic effects of Speedy/RINGO and discusses how this protective function can possibly be exploited to facilitate recovery from SCI.Particular attention is paid to reversal of the negative effects on the ERK/MAPK and PI3K/AKT pathways via induction of p53.

关 键 词：Speedy/RINGO CALPAIN p53 extracellular signal-regulated kinase/mitogen-activated protein kinase phosphoinositide 3-kinase/protein kinase B spinal cord injury glutamate excitotoxicity calcium influx 

分 类 号：R73[医药卫生—肿瘤]