Abstract
Alzheimer’s disease (AD) is the most common form of dementia occurring in the elderly. Several hypotheses have been proposed to explain the pathophysiology of AD, including amyloidogenesis, disruption of calcium homeostasis, energetic failure, induction of oxidative stress, and hyperphosphorylation of tau protein. This review examines associations between cellular and subcellular injuries, neurodegeneration, and cell death in experimental models, clinical symptoms, and autopsy reports of AD to identify the subcellular events leading to disease onset and progression. The order in which these events occur is discussed. The first injuries reported in AD are subcellular and occur at the Golgi apparatus before any β-amyloid proteins deposit in the Golgi and endosomes. This is followed by lysosomal alterations and the inability of cells to clear β-amyloid. The next stage reveals functional changes and modifications in hippocampal synaptic transmission before structural changes are observed at the cellular level. Subsequently, an extensive intracellular inflammatory process develops in neurons and astrocytes. This inflammatory reaction begins in the nucleus, endoplasmic reticulum, endosomes and mitochondria, and is thought to lead to neurodegeneration and cell death. Finally, the neuroinflammatory response of chronically activated microglia escalates the neurodegeneration and cell death. Identifying the detailed sequence of subcellular events induced by the primum movens defect in AD may lead to the identification of novel drug targets for the treatment of the disease.
Keywords: Alzheimer's disease, β-amyloid, endoplasmic reticulum, Golgi, lysosomes, mitochondria, neurons, nucleus, plasma membrane.
CNS & Neurological Disorders - Drug Targets
Title:Subcellular Injuries in Alzheimer's Disease
Volume: 13 Issue: 4
Author(s): Jean-Paul Tillement and Vassilios Papadopoulos
Affiliation:
Keywords: Alzheimer's disease, β-amyloid, endoplasmic reticulum, Golgi, lysosomes, mitochondria, neurons, nucleus, plasma membrane.
Abstract: Alzheimer’s disease (AD) is the most common form of dementia occurring in the elderly. Several hypotheses have been proposed to explain the pathophysiology of AD, including amyloidogenesis, disruption of calcium homeostasis, energetic failure, induction of oxidative stress, and hyperphosphorylation of tau protein. This review examines associations between cellular and subcellular injuries, neurodegeneration, and cell death in experimental models, clinical symptoms, and autopsy reports of AD to identify the subcellular events leading to disease onset and progression. The order in which these events occur is discussed. The first injuries reported in AD are subcellular and occur at the Golgi apparatus before any β-amyloid proteins deposit in the Golgi and endosomes. This is followed by lysosomal alterations and the inability of cells to clear β-amyloid. The next stage reveals functional changes and modifications in hippocampal synaptic transmission before structural changes are observed at the cellular level. Subsequently, an extensive intracellular inflammatory process develops in neurons and astrocytes. This inflammatory reaction begins in the nucleus, endoplasmic reticulum, endosomes and mitochondria, and is thought to lead to neurodegeneration and cell death. Finally, the neuroinflammatory response of chronically activated microglia escalates the neurodegeneration and cell death. Identifying the detailed sequence of subcellular events induced by the primum movens defect in AD may lead to the identification of novel drug targets for the treatment of the disease.
Export Options
About this article
Cite this article as:
Tillement Jean-Paul and Papadopoulos Vassilios, Subcellular Injuries in Alzheimer's Disease, CNS & Neurological Disorders - Drug Targets 2014; 13 (4) . https://dx.doi.org/10.2174/18715273113126660197
DOI https://dx.doi.org/10.2174/18715273113126660197 |
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
-
On the Relationship Between the Light/Dark Cycle, Melatonin and Oxidative Stress
Current Pharmaceutical Design Role of Free Radicals and Poly(ADP-Ribose)Polymerase-1 in the Development of Spinal Cord Injury: New Potential Therapeutic Targets
Current Medicinal Chemistry Anti-Oxidants in Parkinson’s Disease Therapy: A Critical Point of View
Current Neuropharmacology Cannabinoid-related Agents in the Treatment of Anxiety Disorders: Current Knowledge and Future Perspectives
Recent Patents on CNS Drug Discovery (Discontinued) Therapeutic Targets in the Ubiquitin-proteasome System for Alzheimer's Disease
Current Enzyme Inhibition Rho-kinase (ROCK) Inhibitors - A Neuroprotective Therapeutic Paradigm with a Focus on Ocular Utility
Current Medicinal Chemistry Proteasome Inhibition: A Promising Strategy for Treating Cancer, but What About Neurotoxicity?
Current Medicinal Chemistry Exploring the Role of Stem Cell Therapy in Treating Neurodegenerative Diseases: Challenges and Current Perspectives
Current Stem Cell Research & Therapy Cross Talk between the Cardiovascular and Nervous Systems:Neurotrophic Effects of Vascular Endothelial Growth Factor (VEGF) and Angiogenic Effects of Nerve Growth Factor (NGF)-Implications in Drug Development
Current Pharmaceutical Design Denouement of Chemicals on Amyotrophic Lateral Sclerosis: Is Green Chemistry the Answer
Medicinal Chemistry Aluminum Induced Immunoexcitotoxicity in Neurodevelopmental and Neurodegenerative Disorders
Current Inorganic Chemistry (Discontinued) Biphasic Mechanisms of Neurovascular Unit Injury and Protection in CNS Diseases
CNS & Neurological Disorders - Drug Targets Oxidative Imbalance and Anxiety Disorders
Current Neuropharmacology Targeting Glia Cells: Novel Perspectives for the Treatment of Neuropsychiatric Diseases
Current Neuropharmacology The Molecular Basis of Memantine Action in Alzheimers Disease and Other Neurologic Disorders: Low-affinity, Uncompetitive Antagonism
Current Alzheimer Research Therapeutic Potential of Janus Kinase 3 (JAK3) Inhibitors
Current Pharmaceutical Design Non-Antidepressant Pharmacological Treatment of Obsessive Compulsive Disorder: A Comprehensive Review
Current Clinical Pharmacology The Extra-Hematopoietic Role of Erythropoietin in Diabetes Mellitus
Current Diabetes Reviews In vitro Generated Mesenchymal Stem Cells: Suitable Tools to Target Insulin Dependent Diabetes Mellitus?
Current Stem Cell Research & Therapy Contrasting Roles of the Galectin-3 in the Schizophrenia Onset, Clinical Presentation, and Somatic Comorbidity
Current Topics in Medicinal Chemistry