Involvement of CHOP, an ER-stress apoptotic mediator, in both human sporadic ALS and ALS model mice

Neurobiology of Disease

Hirotaka Tanaka¹  Yasushi Ito²  Kazunari Aida²  Masamitsu Shimazawa²  Kazuhiro Tsuruma²  Isao Hozumi²  Mitsunori Yamada³  Takashi Inuzuka⁴  Hitoshi Takahashi⁴  Hideaki Hara⁵ 

[1] Department of Pathology, Brain Research Institute, Niigata University, 1-757, Asahimachi-dori, Chuo-ku, Niigata 951-8585, Japan;Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan;Department of Clinical Research, National Hospital Organization, Saigata National Hospital, 468-1 Saigata, Ohgata-ku Johetsu-city, Niigata 949-3193, Japan;Department of Neurology and Geriatrics, Gifu University Graduate School of Medicine, 1-1, Yanagido, Gifu 501-1194, Japan;Department of Pathology, Brain Research Institute, Niigata University, 1-757, Asahimachi-dori, Chuo-ku, Niigata 951-8585, Japan;

关键词: Amyotrophic lateral sclerosis (ALS);    Astrocyte;    C/EBP homologous protein (CHOP);    Endoplasmic reticulum (ER) stress;    Superoxide dismutase 1 (SOD1);    Spinal cord;   

DOI  :  

来源: DOAJ

【 摘 要 】

Endoplasmic reticulum (ER) stress-induced neuronal death may play a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS). However, whether CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP), an ER-stress apoptotic mediator, is involved in the pathogenesis of ALS is controversial. Here we demonstrate the expression levels and localization of CHOP in spinal cords of both sporadic ALS patients and ALS transgenic mice by immunohistochemistry. In the spinal cords of sporadic ALS patients, CHOP was markedly up-regulated but typically expressed at low levels in those of the control. Likewise, CHOP expression increased at 14 (symptomatic stage) and 18 to 20  weeks (end stage) in ALS transgenic mice spinal cords. Furthermore, localizations of CHOP were merged in motor neurons and glial cells, such as oligodendrocytes, astrocytes, and microglia. These results indicate that the up-regulation of CHOP in motor neurons and glial cells may play pivotal roles in the pathogenesis of ALS.

【 授权许可】

Unknown