Abstract
To date, the beta amyloid (Aβ) cascade hypothesis remains the main pathogenetic model of Alzheimers disease (AD), but its role in the majority of sporadic AD cases is unclear. The mitochondria play central role in the bioenergetics of the cell and apoptotic cell death. In the past 20 years research has been directed at clarifying the involvement of mitochondria and defects in mitochondrial oxidative phosphorylation in late-onset neurodegenerative disorders, including AD. Morphological, biochemical and genetic abnormalities of the mitochondria in several AD tissues have been reported. Impaired mitochondrial respiration, particularly COX deficiency, has been observed in brain, platelets and fibroblasts of AD patients. The “mitochondrial cascade hypothesis” could explain many of the biochemical, genetic and pathological features of sporadic AD. Somatic mutations in mitochondrial DNA (mtDNA) could cause energy failure, increased oxidative stress and accumulation of Aβ, which in a vicious cycle reinforces the mtDNA damage and the oxidative stress. Despite the evidence of mitochondrial dysfunction in AD, no causative mutations in the mtDNA have been detected so far. Indeed, results of studies on the role of mtDNA haplogroups in AD are controversial. In this review we discuss the role of the mitochondria in the cascade of events leading to AD, and we will try to provide an answer to the question “what comes first”.
Keywords: Alzheimer's disease, haplogroups, mitochondria, mtDNA, neurodegeneration
Current Alzheimer Research
Title: Mitochondria, Mitochondrial DNA and Alzheimers Disease. What Comes First?
Volume: 5 Issue: 5
Author(s): Michelangelo Mancuso, Daniele Orsucci, Gabiele Siciliano and Luigi Murri
Affiliation:
Keywords: Alzheimer's disease, haplogroups, mitochondria, mtDNA, neurodegeneration
Abstract: To date, the beta amyloid (Aβ) cascade hypothesis remains the main pathogenetic model of Alzheimers disease (AD), but its role in the majority of sporadic AD cases is unclear. The mitochondria play central role in the bioenergetics of the cell and apoptotic cell death. In the past 20 years research has been directed at clarifying the involvement of mitochondria and defects in mitochondrial oxidative phosphorylation in late-onset neurodegenerative disorders, including AD. Morphological, biochemical and genetic abnormalities of the mitochondria in several AD tissues have been reported. Impaired mitochondrial respiration, particularly COX deficiency, has been observed in brain, platelets and fibroblasts of AD patients. The “mitochondrial cascade hypothesis” could explain many of the biochemical, genetic and pathological features of sporadic AD. Somatic mutations in mitochondrial DNA (mtDNA) could cause energy failure, increased oxidative stress and accumulation of Aβ, which in a vicious cycle reinforces the mtDNA damage and the oxidative stress. Despite the evidence of mitochondrial dysfunction in AD, no causative mutations in the mtDNA have been detected so far. Indeed, results of studies on the role of mtDNA haplogroups in AD are controversial. In this review we discuss the role of the mitochondria in the cascade of events leading to AD, and we will try to provide an answer to the question “what comes first”.
Export Options
About this article
Cite this article as:
Mancuso Michelangelo, Orsucci Daniele, Siciliano Gabiele and Murri Luigi, Mitochondria, Mitochondrial DNA and Alzheimers Disease. What Comes First?, Current Alzheimer Research 2008; 5 (5) . https://dx.doi.org/10.2174/156720508785908946
DOI https://dx.doi.org/10.2174/156720508785908946 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
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
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
- Author Guidelines
- 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
-
Preventing the Spread of Alzheimer’s Disease Neuropathology: A Role for Calcilytics?
Current Pharmaceutical Biotechnology Mesenchymal Stem Cells as a Source of Dopaminergic Neurons: A Potential Cell Based Therapy for Parkinson's Disease
Current Stem Cell Research & Therapy Exploiting the Diversity of the Heat-Shock Protein Family for Primary and Secondary Tauopathy Therapeutics
Current Neuropharmacology Restriction Factors Against Recombinant Adeno-associated Virus Vectormediated Gene Transfer in Dystrophin-deficient Muscles
Current Gene Therapy An Update on the Recent Advances in Cubosome: A Novel Drug Delivery System
Current Drug Metabolism Heat Shock Proteins Protect Against Ischemia and Inflammation Through Multiple Mechanisms
Inflammation & Allergy - Drug Targets (Discontinued) Adult Neurogenesis and the Diseased Brain
Current Medicinal Chemistry Editorial (Thematic Issue: NeuroAIDS: Past, Present and Future)
Current HIV Research Patent Selections :
Recent Patents on CNS Drug Discovery (Discontinued) Recent Developments in Cholinesterases Inhibitors for Alzheimers Disease Treatment
Current Medicinal Chemistry Pathophysiology of Transmissible Spongiform Encephalopathies
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Clinical Applications of Myostatin Inhibitors for Neuromuscular Diseases
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Pathways of Acetylcholine Synthesis, Transport and Release as Targets for Treatment of Adult-Onset Cognitive Dysfunction
Current Medicinal Chemistry Melatonin Metabolism in the Central Nervous System
Current Neuropharmacology APP Transgenic Mouse Models and their Use in Drug Discovery to Evaluate Amyloid-β Lowering Therapeutics
CNS & Neurological Disorders - Drug Targets Tyrosine Kinases as New Molecular Targets in Treatment of Inflammatory Disorders and Leukemia
Current Pharmaceutical Design Resolution-Associated Molecular Patterns (RAMPs) as Endogenous Regulators of Glia Functions in Neuroinflammatory Disease
CNS & Neurological Disorders - Drug Targets Nanowired Drug Delivery Across the Blood-Brain Barrier in Central Nervous System Injury and Repair
CNS & Neurological Disorders - Drug Targets Primary Progressive Aphasia-Defining Genetic and Pathological Subtypes
Current Alzheimer Research Role of Caspases in Activation-Induced Cell Death of Neuroglia
Current Enzyme Inhibition