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Energy Metabolism Decline in the Aging Brain—Pathogenesis of Neurodegenerative Disorders

There is a growing body of evidencethat indicates that the aging of the brain results from the decline of energy metabolism. In particular, the neuronal metabolism of glucose declines steadily, resulting in a growing deficit of adenosine triphosphate (ATP) production—which, in turn, limits glucose a...

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Autor principal: Błaszczyk, Janusz Wiesław
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695180/
https://www.ncbi.nlm.nih.gov/pubmed/33171879
http://dx.doi.org/10.3390/metabo10110450
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author Błaszczyk, Janusz Wiesław
author_facet Błaszczyk, Janusz Wiesław
author_sort Błaszczyk, Janusz Wiesław
collection PubMed
description There is a growing body of evidencethat indicates that the aging of the brain results from the decline of energy metabolism. In particular, the neuronal metabolism of glucose declines steadily, resulting in a growing deficit of adenosine triphosphate (ATP) production—which, in turn, limits glucose access. This vicious circle of energy metabolism at the cellular level is evoked by a rising deficiency of nicotinamide adenine dinucleotide (NAD) in the mitochondrial salvage pathway and subsequent impairment of the Krebs cycle. A decreasing NAD level also impoverishes the activity of NAD-dependent enzymes that augments genetic errors and initiate processes of neuronal degeneration and death.This sequence of events is characteristic of several brain structures in which neurons have the highest energy metabolism. Neurons of the cerebral cortex and basal ganglia with long unmyelinated axons and these with numerous synaptic junctions are particularly prone to senescence and neurodegeneration. Unfortunately, functional deficits of neurodegeneration are initially well-compensated, therefore, clinical symptoms are recognized too late when the damages to the brain structures are already irreversible. Therefore, future treatment strategies in neurodegenerative disorders should focus on energy metabolism and compensation age-related NAD deficit in neurons. This review summarizes the complex interrelationships between metabolic processes on the systemic and cellular levels and provides directions on how to reduce the risk of neurodegeneration and protect the elderly against neurodegenerative diseases.
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spelling pubmed-76951802020-11-28 Energy Metabolism Decline in the Aging Brain—Pathogenesis of Neurodegenerative Disorders Błaszczyk, Janusz Wiesław Metabolites Review There is a growing body of evidencethat indicates that the aging of the brain results from the decline of energy metabolism. In particular, the neuronal metabolism of glucose declines steadily, resulting in a growing deficit of adenosine triphosphate (ATP) production—which, in turn, limits glucose access. This vicious circle of energy metabolism at the cellular level is evoked by a rising deficiency of nicotinamide adenine dinucleotide (NAD) in the mitochondrial salvage pathway and subsequent impairment of the Krebs cycle. A decreasing NAD level also impoverishes the activity of NAD-dependent enzymes that augments genetic errors and initiate processes of neuronal degeneration and death.This sequence of events is characteristic of several brain structures in which neurons have the highest energy metabolism. Neurons of the cerebral cortex and basal ganglia with long unmyelinated axons and these with numerous synaptic junctions are particularly prone to senescence and neurodegeneration. Unfortunately, functional deficits of neurodegeneration are initially well-compensated, therefore, clinical symptoms are recognized too late when the damages to the brain structures are already irreversible. Therefore, future treatment strategies in neurodegenerative disorders should focus on energy metabolism and compensation age-related NAD deficit in neurons. This review summarizes the complex interrelationships between metabolic processes on the systemic and cellular levels and provides directions on how to reduce the risk of neurodegeneration and protect the elderly against neurodegenerative diseases. MDPI 2020-11-07 /pmc/articles/PMC7695180/ /pubmed/33171879 http://dx.doi.org/10.3390/metabo10110450 Text en © 2020 by the author. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Błaszczyk, Janusz Wiesław
Energy Metabolism Decline in the Aging Brain—Pathogenesis of Neurodegenerative Disorders
title Energy Metabolism Decline in the Aging Brain—Pathogenesis of Neurodegenerative Disorders
title_full Energy Metabolism Decline in the Aging Brain—Pathogenesis of Neurodegenerative Disorders
title_fullStr Energy Metabolism Decline in the Aging Brain—Pathogenesis of Neurodegenerative Disorders
title_full_unstemmed Energy Metabolism Decline in the Aging Brain—Pathogenesis of Neurodegenerative Disorders
title_short Energy Metabolism Decline in the Aging Brain—Pathogenesis of Neurodegenerative Disorders
title_sort energy metabolism decline in the aging brain—pathogenesis of neurodegenerative disorders
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695180/
https://www.ncbi.nlm.nih.gov/pubmed/33171879
http://dx.doi.org/10.3390/metabo10110450
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