Mitochondria: The Common Upstream Driver of Amyloid-beta and Tau Pathology in Alzheimer's Disease

作者：Silva D F F; Esteves A R; Oliveira C R; Cardoso S M^*

来源：Current Alzheimer Research, 2011, 8(5): 563-572.

• Alzheimer's disease
• amyloid-beta
• autophagy
• microtubule network
• mitochondria
• tau

Mitochondrial dysfunction has been widely implicated in the etiology of Alzheimer's disease (AD). Evidence shows a mitochondrial-mediated impairment of autophagy that potentiates amyloid-beta(A beta) deposition. Accordingly, recent data obtained from AD models, in which mitochondrial alterations are a prominent feature, demonstrated abnormalities in microtubule network, involving tubulin and tau post-translational modifications. In this review we will discuss mitochondrial-regulated processes where mitochondrial malfunction is likely to start a sequence of events leading to sirtuin-2 activation, microtubule network breakdown, and impairment of the autophagic pathway. Because sirtuin-2 activity depends on cellular NAD(+) availability, mitochondrial regulation of NAD(+) levels may contribute to an increase in sirtuin-mediated tubulin deacetylation. A vicious cycle become installed which potentiates tau hyperphosphorylation, together with A overproduction and deposition. Overall, targeting microtubule network constitutes a promising strategy for pharmacological therapy in AD.

• 出版日期2011-8