Abstract
Vascular and metabolic dysfunctions and mitochondrial failure are now believed to be contributors to Alzheimer’s disease (AD) pathogenesis. Vascular dysfunction includes reduced cerebral blood flow (CBF), blood-brain barrier (BBB) disturbances and cerebral amyloid angiopathy (CAA). Mitochondrial failure results in deregulation of Ca2+ homeostasis and elevated reactive oxygen species (ROS) generation, both of which are linked to neurotoxicity. Increased levels of ROS stimulate proinflammatory gene transcription and release of cytokines, such as IL-1, IL-6, and TNF-α, and chemokines, thereby inducing neuroinflammation. Conversely, inflammatory reactions activate microglia and astrocytes to generate large amounts of ROS, so neuroinflammation could be perceived as a cause and a consequence of chronic oxidative stress. The interaction between oxidative stress and neuroinflammation leads to amyloid-β (Aβ) generation. The deposition of Aβ peptide in the brain generates a cascade of pathological events, including the formation of neurofibrillary tangles (NFTs), inflammatory reactions, increased oxidative stress and mitochondrial dysfunction, which are causative factors of cell death and dementia. The purpose of this paper is to provide current evidence on vascular dysfunction and mitochondrial failure, both in neurons and glia and in brain vascular wall cells in the context of potential application for treatment of AD and other neurodegenerations.
Keywords: Alzheimer's disease, mitochondrial failure, neurodegeneration, neuroinflammation, ROS, vascular dysfunction.
CNS & Neurological Disorders - Drug Targets
Title:Vascular Oxidative Stress and Mitochondrial Failure in the Pathobiology of Alzheimer’s Disease: A New Approach to Therapy
Volume: 12 Issue: 6
Author(s): Marta Sochocka, Euphrosyni S. Koutsouraki, Kazimierz Gasiorowski and Jerzy Leszek
Affiliation:
Keywords: Alzheimer's disease, mitochondrial failure, neurodegeneration, neuroinflammation, ROS, vascular dysfunction.
Abstract: Vascular and metabolic dysfunctions and mitochondrial failure are now believed to be contributors to Alzheimer’s disease (AD) pathogenesis. Vascular dysfunction includes reduced cerebral blood flow (CBF), blood-brain barrier (BBB) disturbances and cerebral amyloid angiopathy (CAA). Mitochondrial failure results in deregulation of Ca2+ homeostasis and elevated reactive oxygen species (ROS) generation, both of which are linked to neurotoxicity. Increased levels of ROS stimulate proinflammatory gene transcription and release of cytokines, such as IL-1, IL-6, and TNF-α, and chemokines, thereby inducing neuroinflammation. Conversely, inflammatory reactions activate microglia and astrocytes to generate large amounts of ROS, so neuroinflammation could be perceived as a cause and a consequence of chronic oxidative stress. The interaction between oxidative stress and neuroinflammation leads to amyloid-β (Aβ) generation. The deposition of Aβ peptide in the brain generates a cascade of pathological events, including the formation of neurofibrillary tangles (NFTs), inflammatory reactions, increased oxidative stress and mitochondrial dysfunction, which are causative factors of cell death and dementia. The purpose of this paper is to provide current evidence on vascular dysfunction and mitochondrial failure, both in neurons and glia and in brain vascular wall cells in the context of potential application for treatment of AD and other neurodegenerations.
Export Options
About this article
Cite this article as:
Sochocka Marta, Koutsouraki S. Euphrosyni, Gasiorowski Kazimierz and Leszek Jerzy, Vascular Oxidative Stress and Mitochondrial Failure in the Pathobiology of Alzheimer’s Disease: A New Approach to Therapy, CNS & Neurological Disorders - Drug Targets 2013; 12 (6) . https://dx.doi.org/10.2174/18715273113129990072
DOI https://dx.doi.org/10.2174/18715273113129990072 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...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
Related Articles
-
Editorial [Hot Topic:Active and Passive Aβ-Immunotherapy: Preclinical and Clinical Studies and Future Directions: Part I (Guest Editors: Michael G. Agadjanyan and David H. Cribbs)]
CNS & Neurological Disorders - Drug Targets BDNF Serum Concentrations Show No Relationship with Diagnostic Group or Medication Status in Neurodegenerative Disease
Current Alzheimer Research An Integrated Approach to Fragment-Based Lead Generation:Philosophy, Strategy and Case Studies from AstraZenecas Drug Discovery Programmes
Current Topics in Medicinal Chemistry Understanding the Global Problem of Drug Addiction is a Challenge for IDARS Scientists
Current Neuropharmacology Role of Glycosphingolipids and Therapeutic Perspectives on Alzheimers Disease
CNS & Neurological Disorders - Drug Targets MicroRNA: Implications for Alzheimer Disease and other Human CNS Disorders
Current Genomics Meet the Editorial Board:
Central Nervous System Agents in Medicinal Chemistry Design, Synthesis and Biological Evaluation of New Cycloalkyl Fused Quinolines Tethered to Isatin Schiff Bases as Cholinesterase Inhibitors
Combinatorial Chemistry & High Throughput Screening Radix Angelica Sinensis Promotes Synaptic Plasticity During Cognitive Recovery in Chronically Stressed Rats
Current Neurovascular Research Inhibition of β-Amyloid Aggregation by Albiflorin, Aloeemodin and Neohesperidin and their Neuroprotective Effect on Primary Hippocampal Cells Against β-Amyloid Induced Toxicity
Current Alzheimer Research The Therapeutical Potential of Alpha-Synuclein Antiaggregatory Agents for Dementia with Lewy Bodies
Current Medicinal Chemistry Antioxidant Properties of Nitric Oxide in Cellular Physiological and Pathophysiological Mechanisms. The Implications of Biological Balance between NO and Oxidative Stress
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Prevalence, Incidence, Risk and Protective Factors of Amnestic Mild Cognitive Impairment in the Elderly in Shanghai
Current Alzheimer Research Biomarkers for Alzheimer's Disease Diagnosis
Current Alzheimer Research Cybernetic Principles of Aging and Rejuvenation: The Buffering- Challenging Strategy for Life Extension
Current Aging Science Role of Central and Peripheral Chemoreceptors in Vasopressin Secretion Control
Endocrine, Metabolic & Immune Disorders - Drug Targets Molecular Targets of Tannic Acid in Alzheimer's Disease
Current Alzheimer Research Metabolic Syndrome: Clinical Features Leading to Therapeutic Strategies
Vascular Disease Prevention (Discontinued) ACAT1 as a Therapeutic Target and its Genetic Relationship with Alzheimer's Disease
Current Alzheimer Research Gestational Programming of Offspring Obesity: A Potential Contributor to Alzheimers Disease
Current Alzheimer Research