| Autor: |
F.F. Silva, D., R. Esteves, A., R. Oliveira, C., M. Cardoso, S. |
| Zdroj: |
Current Alzheimer Research; August 2011, Vol. 8 Issue: 5 p563-572, 10p |
| Abstrakt: |
Mitochondrial dysfunction has been widely implicated in the etiology of Alzheimers disease (AD). Evidence shows a mitochondrial-mediated impairment of autophagy that potentiates amyloid- (A) 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 sirtuinmediated 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. |
| Databáze: |
Supplemental Index |
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