Medicine and Health

Mitochondrial ubiquitin ligase alleviates Alzheimer's disease pathology via blocking the toxic amyloid-β oligomer generation

K. Takeda, A. Uda, et al.

Discover how mitochondrial dynamics play a crucial role in Alzheimer's disease in this groundbreaking research led by Keisuke Takeda and colleagues. Their study reveals the downregulation of the mitochondrial ubiquitin ligase MITOL/MARCH5 in AD patients, exacerbating cognitive decline and mitochondrial dysfunction. This groundbreaking work links mitochondrial changes to increased toxic Aβ oligomer production, reshaping our understanding of AD pathogenesis.

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Abstract

Mitochondrial pathophysiology is implicated in Alzheimer's disease (AD). This study finds that MITOL/MARCH5, a mitochondrial ubiquitin ligase regulating mitochondrial dynamics, is downregulated in AD patients. MITOL deletion in an AD mouse model exacerbated cognitive decline and mitochondrial impairments. This was linked to increased production of toxic Aβ oligomers due to enhanced seeding by Aβ fibrils, rather than increased Aβ plaque formation. The findings suggest that mitochondrial morphology alterations direct Aβ aggregation towards oligomers, a key factor in AD pathogenesis.

Publisher

Communications Biology

Published On

Feb 12, 2021

Authors

Keisuke Takeda, Aoi Uda, Mikihiro Mitsubori, Shun Nagashima, Hiroko Iwasaki, Naoki Ito, Isshin Shiiba, Satoshi Ishido, Masaaki Matsuoka, Ryoko Inatome, Shigeru Yanagi

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