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This review explores the metabolic intricacies of astrocytes in both physiological and pathological conditions, highlighting their adaptive plasticity and diverse functions. Under normal conditions, astrocytes modulate synaptic activity, recycle neurotransmitters, and maintain the blood\u2013brain barrier, ensuring a balanced energy supply and protection against oxidative stress. However, in response to central nervous system pathologies such as neurotrauma, stroke, infections, and neurodegenerative diseases like Alzheimer\u2019s and Huntington\u2019s disease, astrocytes undergo significant morphological, molecular, and metabolic changes. Reactive astrocytes upregulate glycolysis and fatty acid oxidation to meet increased energy demands, which can be protective in acute settings but may exacerbate chronic inflammation and disease progression. This review emphasizes the need for advanced molecular, genetic, and physiological tools to further understand astrocyte heterogeneity and their metabolic reprogramming in disease states.<\/jats:p>","DOI":"10.3390\/ijms25168922","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T06:23:20Z","timestamp":1723789400000},"page":"8922","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Metabolic Reprogramming of Astrocytes in Pathological Conditions: Implications for Neurodegenerative Diseases"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4856-0835","authenticated-orcid":false,"given":"Corrado","family":"Cal\u00ec","sequence":"first","affiliation":[{"name":"Department of Neuroscience \u201cRita Levi Montalcini\u201d, University of Turin, 10124 Turin, Italy"},{"name":"Neuroscience Institute Cavalieri Ottolenghi, 10143 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iva","family":"Cantando","sequence":"additional","affiliation":[{"name":"Department of Fundamental Neurosciences (DNF), University of Lausanne (UNIL), 1005 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4635-4192","authenticated-orcid":false,"given":"Maria Fernanda","family":"Veloz Castillo","sequence":"additional","affiliation":[{"name":"Department of Neuroscience \u201cRita Levi Montalcini\u201d, University of Turin, 10124 Turin, Italy"},{"name":"Neuroscience Institute Cavalieri Ottolenghi, 10143 Orbassano, Italy"},{"name":"Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3842-637X","authenticated-orcid":false,"given":"Laurine","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Department of Fundamental Neurosciences (DNF), University of Lausanne (UNIL), 1005 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8279-3600","authenticated-orcid":false,"given":"Paola","family":"Bezzi","sequence":"additional","affiliation":[{"name":"Department of Fundamental Neurosciences (DNF), University of Lausanne (UNIL), 1005 Lausanne, Switzerland"},{"name":"Department of Physiology and Pharmacology, University of Rome Sapienza, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,16]]},"reference":[{"key":"ref_1","unstructured":"Clarke, D.D., and Sokoloff, L. 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