Metabolism navigates neural cell fate in development, aging and neurodegeneration
Autor: | Jessica Lagerwall, Sophie Eichhorner, Larissa Traxler, Jerome Mertens, Davide Stefanoni, Angelo D'Alessandro |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Aging Neurodegenerative Disorders Neuroscience (miscellaneous) Medicine (miscellaneous) Review Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Immunology and Microbiology (miscellaneous) Alzheimer Disease Pathology medicine RB1-214 Humans Epigenetics Neural cell Neurons Mechanism (biology) Stem Cells Neurodegeneration Brain Psychiatric disorder Human brain medicine.disease 3. Good health Metabolic pathway 030104 developmental biology medicine.anatomical_structure Brain aging Neural development Metabolic Disorders Cell Fate Control Metabolic state Medicine Energy Metabolism Neuroscience 030217 neurology & neurosurgery |
Zdroj: | Disease Models & Mechanisms article-version (VoR) Version of Record Disease Models & Mechanisms, Vol 14, Iss 8 (2021) |
ISSN: | 1754-8411 1754-8403 |
DOI: | 10.1242/dmm.048993 |
Popis: | An uninterrupted energy supply is critical for the optimal functioning of all our organs, and in this regard the human brain is particularly energy dependent. The study of energy metabolic pathways is a major focus within neuroscience research, which is supported by genetic defects in the oxidative phosphorylation mechanism often contributing towards neurodevelopmental disorders and changes in glucose metabolism presenting as a hallmark feature in age-dependent neurodegenerative disorders. However, as recent studies have illuminated roles of cellular metabolism that span far beyond mere energetics, it would be valuable to first comprehend the physiological involvement of metabolic pathways in neural cell fate and function, and to subsequently reconstruct their impact on diseases of the brain. In this Review, we first discuss recent evidence that implies metabolism as a master regulator of cell identity during neural development. Additionally, we examine the cell type-dependent metabolic states present in the adult brain. As metabolic states have been studied extensively as crucial regulators of malignant transformation in cancer, we reveal how knowledge gained from the field of cancer has aided our understanding in how metabolism likewise controls neural fate determination and stability by directly wiring into the cellular epigenetic landscape. We further summarize research pertaining to the interplay between metabolic alterations and neurodevelopmental and psychiatric disorders, and expose how an improved understanding of metabolic cell fate control might assist in the development of new concepts to combat age-dependent neurodegenerative diseases, particularly Alzheimer's disease. Summary: Distinct metabolic states regulate the identity of neural cells during development and adulthood. Metabolic alterations due to changes in nutrient availability and aging destabilize cell identity and contribute to neurological diseases. |
Databáze: | OpenAIRE |
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