A Golgi fragmentation pathway in neurodegeneration

NEUROBIOLOGY OF DISEASE

卷:29

Article

Nakagomi, Saya¹  Barsoum, Mark J.¹  Bossy-Wetzel, Ella^1,2  Suetterlin, Christine³  Malhotra, Vivek³  Lipton, Stuart A.^1,4 

[1] Burnham Inst Med Res, Ctr Neurosci Aging & Stem Cell Res, La Jolla, CA 92037 USA

[2] Burnham Inst Med Res, Program Apoptosis, La Jolla, CA 92037 USA

[3] Univ Calif San Diego, La Jolla, CA 92039 USA

[4] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92039 USA

关键词: Golgi fragmentation;    ER stress;    apoptosis;    mitochondria;    Alzheimer's disease;    amyotrophic lateral sclerosis;    excitotoxicity;    NMDA;    oxidative stress;    nitrosative stress;   

DOI  :  10.1016/j.nbd.2007.08.015

来源: Elsevier

【 摘 要 】

The Golgi apparatus processes intracellular proteins, but undergoes disassembly and fragmentation during apoptosis in several neurodegenerative disorders such as amyotrophic lateral sclerosis and Alzheimer's disease. It is well known that other cytoplasmic organelles play important roles in cell death pathways. Thus, we hypothesized that Golgi fragmentation might participate in transduction of cell death signals. Here, we found that Golgi fragmentation and dispersal precede neuronal cell death triggered by excitotoxins, oxidative/nitrosative insults, or ER stress. Pharmacological intervention or overexpression of the C-terminal fragment of Grasp65, a Golgi-associated protein, inhibits fragmentation and decreases or delays neuronal cell death. Inhibition of mitochondrial or ER cell death pathways also decreases Golgi fragmentation, indicating crosstalk between organelles and suggesting that the Golgi may be a common downstream-effector of cell death. Taken together, these findings implicate the Golgi as a sensor of stress signals in cell death pathways. (C) 2007 Elsevier Inc. All rights reserved.

【 授权许可】

Free