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A Bird’s-Eye View of the Multiple Biochemical Mechanisms that Propel Pathology of Alzheimer’s Disease: Recent Advances and Mechanistic Perspectives on How to Halt the Disease Progression Targeting Multiple Pathways

Neurons consume the highest amount of oxygen, depend on oxidative metabolism for energy, and survive for the lifetime of an individual. Therefore, neurons are vulnerable to death caused by oxidative-stress, accumulation of damaged and dysfunctional proteins and organelles. There is an exponential in...

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Autores principales: Vegh, Caleb, Stokes, Kyle, Ma, Dennis, Wear, Darcy, Cohen, Jerome, Ray, Sidhartha D., Pandey, Siyaram
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598003/
https://www.ncbi.nlm.nih.gov/pubmed/31127770
http://dx.doi.org/10.3233/JAD-181230
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author Vegh, Caleb
Stokes, Kyle
Ma, Dennis
Wear, Darcy
Cohen, Jerome
Ray, Sidhartha D.
Pandey, Siyaram
author_facet Vegh, Caleb
Stokes, Kyle
Ma, Dennis
Wear, Darcy
Cohen, Jerome
Ray, Sidhartha D.
Pandey, Siyaram
author_sort Vegh, Caleb
collection PubMed
description Neurons consume the highest amount of oxygen, depend on oxidative metabolism for energy, and survive for the lifetime of an individual. Therefore, neurons are vulnerable to death caused by oxidative-stress, accumulation of damaged and dysfunctional proteins and organelles. There is an exponential increase in the number of patients diagnosed with neurodegenerative diseases such as Alzheimer’s (AD) as the number of elderly increases exponentially. Development of AD pathology is a complex phenomenon characterized by neuronal death, accumulation of extracellular amyloid-β plaques and neurofibrillary tangles, and most importantly loss of memory and cognition. These pathologies are most likely caused by mechanisms including oxidative stress, mitochondrial dysfunction/stress, accumulation of misfolded proteins, and defective organelles due to impaired proteasome and autophagy mechanisms. Currently, there are no effective treatments to halt the progression of this disease. In order to treat this complex disease with multiple biochemical pathways involved, a complex treatment regimen targeting different mechanisms should be investigated. Furthermore, as AD is a progressive disease-causing morbidity over many years, any chemo-modulator for treatment must be used over long period of time. Therefore, treatments must be safe and non-interfering with other processes. Ideally, a treatment like medicinal food or a supplement that can be taken regularly without any side effect capable of reducing oxidative stress, stabilizing mitochondria, activating autophagy or proteasome, and increasing energy levels of neurons would be the best solution. This review summarizes progress in research on different mechanisms of AD development and some of the potential therapeutic development strategies targeting the aforementioned pathologies.
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spelling pubmed-65980032019-07-01 A Bird’s-Eye View of the Multiple Biochemical Mechanisms that Propel Pathology of Alzheimer’s Disease: Recent Advances and Mechanistic Perspectives on How to Halt the Disease Progression Targeting Multiple Pathways Vegh, Caleb Stokes, Kyle Ma, Dennis Wear, Darcy Cohen, Jerome Ray, Sidhartha D. Pandey, Siyaram J Alzheimers Dis Review Neurons consume the highest amount of oxygen, depend on oxidative metabolism for energy, and survive for the lifetime of an individual. Therefore, neurons are vulnerable to death caused by oxidative-stress, accumulation of damaged and dysfunctional proteins and organelles. There is an exponential increase in the number of patients diagnosed with neurodegenerative diseases such as Alzheimer’s (AD) as the number of elderly increases exponentially. Development of AD pathology is a complex phenomenon characterized by neuronal death, accumulation of extracellular amyloid-β plaques and neurofibrillary tangles, and most importantly loss of memory and cognition. These pathologies are most likely caused by mechanisms including oxidative stress, mitochondrial dysfunction/stress, accumulation of misfolded proteins, and defective organelles due to impaired proteasome and autophagy mechanisms. Currently, there are no effective treatments to halt the progression of this disease. In order to treat this complex disease with multiple biochemical pathways involved, a complex treatment regimen targeting different mechanisms should be investigated. Furthermore, as AD is a progressive disease-causing morbidity over many years, any chemo-modulator for treatment must be used over long period of time. Therefore, treatments must be safe and non-interfering with other processes. Ideally, a treatment like medicinal food or a supplement that can be taken regularly without any side effect capable of reducing oxidative stress, stabilizing mitochondria, activating autophagy or proteasome, and increasing energy levels of neurons would be the best solution. This review summarizes progress in research on different mechanisms of AD development and some of the potential therapeutic development strategies targeting the aforementioned pathologies. IOS Press 2019-06-04 /pmc/articles/PMC6598003/ /pubmed/31127770 http://dx.doi.org/10.3233/JAD-181230 Text en © 2019 – IOS Press and the authors. All rights reserved https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Vegh, Caleb
Stokes, Kyle
Ma, Dennis
Wear, Darcy
Cohen, Jerome
Ray, Sidhartha D.
Pandey, Siyaram
A Bird’s-Eye View of the Multiple Biochemical Mechanisms that Propel Pathology of Alzheimer’s Disease: Recent Advances and Mechanistic Perspectives on How to Halt the Disease Progression Targeting Multiple Pathways
title A Bird’s-Eye View of the Multiple Biochemical Mechanisms that Propel Pathology of Alzheimer’s Disease: Recent Advances and Mechanistic Perspectives on How to Halt the Disease Progression Targeting Multiple Pathways
title_full A Bird’s-Eye View of the Multiple Biochemical Mechanisms that Propel Pathology of Alzheimer’s Disease: Recent Advances and Mechanistic Perspectives on How to Halt the Disease Progression Targeting Multiple Pathways
title_fullStr A Bird’s-Eye View of the Multiple Biochemical Mechanisms that Propel Pathology of Alzheimer’s Disease: Recent Advances and Mechanistic Perspectives on How to Halt the Disease Progression Targeting Multiple Pathways
title_full_unstemmed A Bird’s-Eye View of the Multiple Biochemical Mechanisms that Propel Pathology of Alzheimer’s Disease: Recent Advances and Mechanistic Perspectives on How to Halt the Disease Progression Targeting Multiple Pathways
title_short A Bird’s-Eye View of the Multiple Biochemical Mechanisms that Propel Pathology of Alzheimer’s Disease: Recent Advances and Mechanistic Perspectives on How to Halt the Disease Progression Targeting Multiple Pathways
title_sort bird’s-eye view of the multiple biochemical mechanisms that propel pathology of alzheimer’s disease: recent advances and mechanistic perspectives on how to halt the disease progression targeting multiple pathways
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598003/
https://www.ncbi.nlm.nih.gov/pubmed/31127770
http://dx.doi.org/10.3233/JAD-181230
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