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Review
. 2020:155:1-35.
doi: 10.1016/bs.irn.2020.01.009. Epub 2020 Aug 11.

Dysregulation of metabolic flexibility: The impact of mTOR on autophagy in neurodegenerative disease

Kenneth Maiese  1
Affiliations
Review

Dysregulation of metabolic flexibility: The impact of mTOR on autophagy in neurodegenerative disease

Kenneth Maiese. Int Rev Neurobiol. 2020.

Abstract

Non-communicable diseases (NCDs) that involve neurodegenerative disorders and metabolic disease impact over 400 million individuals globally. Interestingly, metabolic disorders, such as diabetes mellitus, are significant risk factors for the development of neurodegenerative diseases. Given that current therapies for these NCDs address symptomatic care, new avenues of discovery are required to offer treatments that affect disease progression. Innovative strategies that fill this void involve the mechanistic target of rapamycin (mTOR) and its associated pathways of mTOR complex 1 (mTORC1), mTOR complex 2 (mTORC2), AMP activated protein kinase (AMPK), trophic factors that include erythropoietin (EPO), and the programmed cell death pathways of autophagy and apoptosis. These pathways are intriguing in their potential to provide effective care for metabolic and neurodegenerative disorders. Yet, future work is necessary to fully comprehend the entire breadth of the mTOR pathways that can effectively and safely translate treatments to clinical medicine without the development of unexpected clinical disabilities.

Keywords: AMPK; Alzheimer's disease; Apoptosis; Autophagy; Dementia; Diabetes mellitus; Erythropoietin; mTOR; mTORC1; mTORC2.

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Figures

Figure 1:
Figure 1:. Novel Therapeutic Avenues with mTOR.
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 the trophic factor erythropoietin offer novel therapeutic avenues to treat neurodegenerative disorders through metabolic pathways. mTOR and its pathways broadly impact metabolic disease and the nervous system through the oversight of programmed cell death pathways of autophagy and apoptosis. Given that current therapies for metabolic disease and neurodegenerative disorders address only symptomatic care, mTOR and its associated pathways provide strong prospects to treat both the onset and progression of metabolic disease in association with neurodegenerative disorders. Yet, it is clear that comprehensive understanding is required to appreciate the large breadth of mTOR pathways to safely translate treatments to clinical medicine without the onset of unexpected clinical disabilities.
See this image and copyright information in PMC

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