Abstract
Mitochondrial dysfunction has been widely implicated in the etiology of Alzheimers disease (AD). Evidence shows a mitochondrial-mediated impairment of autophagy that potentiates amyloid-β (Aβ) 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 Aβ overproduction and deposition. Overall, targeting microtubule network constitutes a promising strategy for pharmacological therapy in AD.
Keywords: Alzheimer's disease, amyloid-β, autophagy, microtubule network, mitochondria, tau, calcium homeostasis, oxidative phosphorylation, AD development, oxidative stress markers, neurodegeneration, mitochondrial integrity, resonance spectroscopy
Current Alzheimer Research
Title: Mitochondria: The Common Upstream Driver of Amyloid-β and Tau Pathology in Alzheimers Disease
Volume: 8 Issue: 5
Author(s): D. F.F. Silva, A. R. Esteves, C. R. Oliveira and S. M. Cardoso
Affiliation:
Keywords: Alzheimer's disease, amyloid-β, autophagy, microtubule network, mitochondria, tau, calcium homeostasis, oxidative phosphorylation, AD development, oxidative stress markers, neurodegeneration, mitochondrial integrity, resonance spectroscopy
Abstract: Mitochondrial dysfunction has been widely implicated in the etiology of Alzheimers disease (AD). Evidence shows a mitochondrial-mediated impairment of autophagy that potentiates amyloid-β (Aβ) 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 Aβ overproduction and deposition. Overall, targeting microtubule network constitutes a promising strategy for pharmacological therapy in AD.
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Cite this article as:
F.F. Silva D., R. Esteves A., R. Oliveira C. and M. Cardoso S., Mitochondria: The Common Upstream Driver of Amyloid-β and Tau Pathology in Alzheimers Disease, Current Alzheimer Research 2011; 8 (5) . https://dx.doi.org/10.2174/156720511796391872
DOI https://dx.doi.org/10.2174/156720511796391872 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
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