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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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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7695180 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT błaszczykjanuszwiesław energymetabolismdeclineintheagingbrainpathogenesisofneurodegenerativedisorders |