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.
Export Options
About this article
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 |
![](/images/wayfinder.jpg)
- Author Guidelines
- Bentham Author Support Services (BASS)
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
New Insights into the Immune Response to Pneumococci
Current Respiratory Medicine Reviews Combined Therapies for Lysosomal Storage Diseases
Current Molecular Medicine Patent Annotations
Recent Patents on Anti-Cancer Drug Discovery Current Understanding of Polymyxin B Applications in Bacteraemia/ Sepsis Therapy Prevention: Clinical, Pharmaceutical, Structural and Mechanistic Aspects
Anti-Infective Agents in Medicinal Chemistry Synthesis and Biological Activity of Unnatural Enediynes
Current Medicinal Chemistry Clinical Signs, Prevention and Treatment of Viral Infections in Infants
Infectious Disorders - Drug Targets Extracellular Enzymes Production and Biofilm Formation in Rhodotorula Species
Current Enzyme Inhibition Histone Deacetylase (HDAC) Inhibitors - emerging roles in neuronal memory, learning, synaptic plasticity and neural regeneration
Current Neuropharmacology Editorial (Thematic Issue: MiRNAcles in the Brain: What to Wish and What to Fear)
CNS & Neurological Disorders - Drug Targets Cefepime-Induced Neurotoxicity
Central Nervous System Agents in Medicinal Chemistry Hypersensitivity Reactions to Quinolones
Current Pharmaceutical Design Neurotransmitter Effects in Human Immunodeficiency Virus (HIV) and Simian Immuno-Deficiency Virus (SIV) Infection
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Novel Targets for the Development of Anti-Herpes Compounds
Infectious Disorders - Drug Targets Commentary (Research Highlights: Transcranial Drug Delivery for Neurological Disorders)
CNS & Neurological Disorders - Drug Targets Targeting the Atypical Chemokine Receptor ACKR3/CXCR7: Phase 1 - Phage Display Peptide Identification and Characterization
Current Topics in Medicinal Chemistry Ivermectin in Human Medicine, An Overview of the Current Status of Its Clinical Applications
Current Pharmaceutical Biotechnology A 30-years Review on Pharmacokinetics of Antibiotics: Is the Right Time for Pharmacogenetics?
Current Drug Metabolism Therapeutic Targeting of Leukocyte Trafficking Across the Blood-Brain Barrier
Inflammation & Allergy - Drug Targets (Discontinued) Significant Breakthroughs in Search for Anti-Infectious Agents Derived from Erythromycin A
Current Medicinal Chemistry Functions of Fukutin, a Gene Responsible for Fukuyama Type Congenital Muscular Dystrophy, in Neuromuscular System and Other Somatic Organs
Central Nervous System Agents in Medicinal Chemistry