Journal
JOURNAL OF NEUROSCIENCE RESEARCH
Volume 86, Issue 14, Pages 3230-3239Publisher
WILEY
DOI: 10.1002/jnr.21760
Keywords
PP2A; LC3; cathepsin; 3-methyladenine; rapamycin
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Autophagosomes are accumulated in Alzheimer's disease (AD), but the regulatory pathway of autophagy in AD remains largely unknown. By using electron microscopy, Western blotting, and immunocytochemistry, here we show that autophagosomes are accumulated in rat neurons by okadaic acid (OA), a protein phosphatase-2A inhibitor known to enhance tan phosphorylation, beta-amyloid (A beta) deposition, and neuronal death, which are the pathological hallmarks of AD. Autophagy can be generally induced via several distinct pathways, such as inhibition of mTOR or activation of beclin-1. Interestingly, OA increased both mTOR and beclin-1 pathways simultaneously, which suggests that autophagy in OA-treated neurons is induced mainly via the beclin-1 pathway, and less so via mTOR inhibition. Finally, inhibition of autophagy by 3MA reduced cytotoxicity in OA-treated neurons. Our novel findings provide new insights into the pathology of and therapeutic intervention for AD. (c) 2008 Wiley-Liss, Inc.
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