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
-
Pathogenesis of and Therapeutic Strategies to Ameliorate the Transthyretin Amyloidoses
Current Pharmaceutical Design Will Antirheumatic Treatment Improve Cardiovascular Outcomes in Patients with Rheumatoid Arthritis?
Current Pharmaceutical Design Cerebrovascular Pathology and Responsiveness to Treatment in Alzheimer’s Disease: A Systematic Review
Current Alzheimer Research Proteins of the Esterase Family: Patents for Some Proteins in Search of Metabolic Functions
Recent Patents on Biomarkers Progression of Alzheimer-type Neurofibrillary Tangles is Related to the Proximodistal Segments of the Hemispheric Arteries
Current Alzheimer Research Alzheimer's Disease and Natural Products: Future Regimens Emerging from Nature
Current Topics in Medicinal Chemistry Subject index to volume 1
Current HIV Research Nicotinamide and its Pharmacological Properties for Clinical Therapy
Drug Design Reviews - Online (Discontinued) Is the Deficiency of Vitamin B12 Related to Oxidative Stress and Neurotoxicity in Parkinsons Patients?
CNS & Neurological Disorders - Drug Targets Pharmacogenetic Aspects of Therapy with Cholinesterase Inhibitors: The Role of CYP2D6 in Alzheimers Disease Pharmacogenetics
Current Alzheimer Research Dopamine Neurotransmission and Atypical Antipsychotics in Prefrontal Cortex: A Critical Review
Current Topics in Medicinal Chemistry The Effects of CCRC on Cognition and Brain Activity in aMCI Patients: A Pilot Placebo Controlled BOLD fMRI Study
Current Alzheimer Research Structural and Functional Impairment of the Retina and Optic Nerve in Alzheimer’s Disease
Current Alzheimer Research Patent on Biomarkers in Medical Research: A Focus on Neuropsychiatric Disorders
Recent Patents on Biomarkers Nanoparticles, Neurotoxicity and Neurodegenerative Diseases
Current Drug Metabolism Lewy Bodies: A Spectator or Salient Killer?
CNS & Neurological Disorders - Drug Targets Parkinson's Disease, Diabetes and Cognitive Impairment
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Review: Alternative Splicing (AS) of Genes As An Approach for Generating Protein Complexity
Current Genomics Modulation of Rack-1/PKCβII Signalling By Soluble AβPPα in SH-SY5Y Cells
Current Alzheimer Research Effect of Synthetic Cannabinoid HU210 on Memory Deficits and Neuropathology in Alzheimers Disease Mouse Model
Current Alzheimer Research