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.
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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 |
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