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Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets
Damage or loss of brain cells and impaired neurochemistry, neurogenesis, and synaptic and nonsynaptic plasticity of the brain lead to dementia in neurodegenerative diseases, such as Alzheimer’s disease (AD). Injury to synapses and neurons and accumulation of extracellular amyloid plaques and intrace...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687482/ https://www.ncbi.nlm.nih.gov/pubmed/36421690 http://dx.doi.org/10.3390/biom12111676 |
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author | Fišar, Zdeněk |
author_facet | Fišar, Zdeněk |
author_sort | Fišar, Zdeněk |
collection | PubMed |
description | Damage or loss of brain cells and impaired neurochemistry, neurogenesis, and synaptic and nonsynaptic plasticity of the brain lead to dementia in neurodegenerative diseases, such as Alzheimer’s disease (AD). Injury to synapses and neurons and accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles are considered the main morphological and neuropathological features of AD. Age, genetic and epigenetic factors, environmental stressors, and lifestyle contribute to the risk of AD onset and progression. These risk factors are associated with structural and functional changes in the brain, leading to cognitive decline. Biomarkers of AD reflect or cause specific changes in brain function, especially changes in pathways associated with neurotransmission, neuroinflammation, bioenergetics, apoptosis, and oxidative and nitrosative stress. Even in the initial stages, AD is associated with Aβ neurotoxicity, mitochondrial dysfunction, and tau neurotoxicity. The integrative amyloid-tau-mitochondrial hypothesis assumes that the primary cause of AD is the neurotoxicity of Aβ oligomers and tau oligomers, mitochondrial dysfunction, and their mutual synergy. For the development of new efficient AD drugs, targeting the elimination of neurotoxicity, mutual potentiation of effects, and unwanted protein interactions of risk factors and biomarkers (mainly Aβ oligomers, tau oligomers, and mitochondrial dysfunction) in the early stage of the disease seems promising. |
format | Online Article Text |
id | pubmed-9687482 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96874822022-11-25 Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets Fišar, Zdeněk Biomolecules Review Damage or loss of brain cells and impaired neurochemistry, neurogenesis, and synaptic and nonsynaptic plasticity of the brain lead to dementia in neurodegenerative diseases, such as Alzheimer’s disease (AD). Injury to synapses and neurons and accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles are considered the main morphological and neuropathological features of AD. Age, genetic and epigenetic factors, environmental stressors, and lifestyle contribute to the risk of AD onset and progression. These risk factors are associated with structural and functional changes in the brain, leading to cognitive decline. Biomarkers of AD reflect or cause specific changes in brain function, especially changes in pathways associated with neurotransmission, neuroinflammation, bioenergetics, apoptosis, and oxidative and nitrosative stress. Even in the initial stages, AD is associated with Aβ neurotoxicity, mitochondrial dysfunction, and tau neurotoxicity. The integrative amyloid-tau-mitochondrial hypothesis assumes that the primary cause of AD is the neurotoxicity of Aβ oligomers and tau oligomers, mitochondrial dysfunction, and their mutual synergy. For the development of new efficient AD drugs, targeting the elimination of neurotoxicity, mutual potentiation of effects, and unwanted protein interactions of risk factors and biomarkers (mainly Aβ oligomers, tau oligomers, and mitochondrial dysfunction) in the early stage of the disease seems promising. MDPI 2022-11-11 /pmc/articles/PMC9687482/ /pubmed/36421690 http://dx.doi.org/10.3390/biom12111676 Text en © 2022 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Fišar, Zdeněk Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets |
title | Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets |
title_full | Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets |
title_fullStr | Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets |
title_full_unstemmed | Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets |
title_short | Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets |
title_sort | linking the amyloid, tau, and mitochondrial hypotheses of alzheimer’s disease and identifying promising drug targets |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687482/ https://www.ncbi.nlm.nih.gov/pubmed/36421690 http://dx.doi.org/10.3390/biom12111676 |
work_keys_str_mv | AT fisarzdenek linkingtheamyloidtauandmitochondrialhypothesesofalzheimersdiseaseandidentifyingpromisingdrugtargets |