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. 2023;20(3):314-333.
doi: 10.2174/1567202620666230721122957.

The Metabolic Basis for Nervous System Dysfunction in Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease

Kenneth Maiese  1
Affiliations

The Metabolic Basis for Nervous System Dysfunction in Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease

Kenneth Maiese. Curr Neurovasc Res. 2023.

Abstract

Disorders of metabolism affect multiple systems throughout the body but may have the greatest impact on both central and peripheral nervous systems. Currently available treatments and behavior changes for disorders that include diabetes mellitus (DM) and nervous system diseases are limited and cannot reverse the disease burden. Greater access to healthcare and a longer lifespan have led to an increased prevalence of metabolic and neurodegenerative disorders. In light of these challenges, innovative studies into the underlying disease pathways offer new treatment perspectives for Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease. Metabolic disorders are intimately tied to neurodegenerative diseases and can lead to debilitating outcomes, such as multi-nervous system disease, susceptibility to viral pathogens, and long-term cognitive disability. Novel strategies that can robustly address metabolic disease and neurodegenerative disorders involve a careful consideration of cellular metabolism, programmed cell death pathways, the mechanistic target of rapamycin (mTOR) and its associated pathways of mTOR Complex 1 (mTORC1), mTOR Complex 2 (mTORC2), AMP-activated protein kinase (AMPK), growth factor signaling, and underlying risk factors such as the apolipoprotein E (APOE-ε4) gene. Yet, these complex pathways necessitate comprehensive understanding to achieve clinical outcomes that target disease susceptibility, onset, and progression.

Keywords: Alzheimer’s disease; COVID-19; Huntington’s disease; Parkinson’s disease; apoptosis; autophagy; diabetes mellitus; erythropoietin; mTOR; pyroptosis.

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Figures

Figure 1:
Figure 1:. Metabolic and Neurodegenerative Disease Cellular Pathways.
A number of metabolic and neurodegenerative cellular pathways rely upon the mechanistic target of rapamycin (mTOR) and its associated pathways of mTOR Complex 1 (mTORC1), mTOR Complex 2 (mTORC2), AMP activated protein kinase (AMPK), and p70 ribosomal S6 kinase (p70S6K). Intimately linked to these pathways are trophic factors, such as erythropoietin (EPO), apoptosis, autophagy, and inflammation that can involve pyroptosis.
Figure 2:
Figure 2:. The Impact of Metabolic Dysfunction on Neurodegenerative Disorders.
Metabolic disorders are tightly linked to the onset and progression of neurodegenerative disorders. These include Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. In addition, other disorders, such as the apolipoprotein E (APOE-ε4) gene and coronavirus disease 2019 (COVID-19) can foster the onset and susceptibility of these neurodegenerative disorders through underlying metabolic pathways.
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