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This review critically evaluates the experimental, epidemiological, and mechanistic evidence linking early-life metabolic and environmental insults with the establishment of latent vulnerability. We propose that this status may remain clinically silent for decades until activated by aging and cumulative stressors, ultimately leading to neurodegeneration. Specifically, we analyze how early metabolic alterations disrupt mitochondrial function, redox signaling, synaptogenesis, and glial programming, particularly in microglia, thereby shaping long-term neuroinflammatory tone and dysfunctional neural circuit maturation. The review highlights the role of the \u03b17 nicotinic acetylcholine receptor (\u03b17nAChR) as a strategic molecular bridge onto which metabolic and inflammatory signals converge. We further discuss how early dysregulatory stressors manifest later in life as dysmetabolism, vascular impairment, and defective energy sensing, all of which accelerate neurodegenerative pathophysiological processes. This life-course perspective reframes these disorders as a continuum and highlights critical prophylactic and\/or therapeutic opportunities through early nutritional, metabolic, and environmental interventions.<\/jats:p>","DOI":"10.3389\/fneur.2026.1860052","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:05:49Z","timestamp":1788534349000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Common metabolic, environmental, and molecular mechanisms underlying neurodevelopmental and neurodegenerative disorders"],"prefix":"10.3389","volume":"17","author":[{"given":"Ana Sof\u00eda","family":"Vall\u00e9s","sequence":"first","affiliation":[{"name":"Laboratorio de Nutrici\u00f3n y Neurodesarrollo, Instituto de Investigaciones Bioqu\u00edmicas de Bah\u00eda Blanca, BByF-UNS-CONICET","place":["Bah\u00eda Blanca, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J.","family":"Barrantes","sequence":"additional","affiliation":[{"name":"Molecular Neurobiology Division, Biomedical Research Institute, UCA-CONICET","place":["Buenos Aires, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1111\/jir.13197","article-title":"High frequency of mitochondrial DNA rearrangements in the peripheral blood of adults with intellectual disability","volume":"69","author":"Bulduk","year":"2025","journal-title":"J Intellect Disabil Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"327","DOI":"10.3390\/biomedicines13020327","article-title":"Mitochondrial dysfunction in neurodegenerative diseases: mechanisms and corresponding therapeutic strategies","volume":"13","author":"Meng","year":"2025","journal-title":"Biomedicines."},{"key":"B3","doi-asserted-by":"publisher","first-page":"105564","DOI":"10.1016\/j.nbd.2021.105564","article-title":"Postsynaptic autism spectrum disorder genes and synaptic dysfunction","volume":"162","author":"Bonsi","year":"2022","journal-title":"Neurobiol Dis."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1129036","DOI":"10.3389\/fnsyn.2023.1129036","article-title":"Alzheimer's disease as a synaptopathy: evidence for dysfunction of synapses during disease progression","volume":"15","author":"Meftah","year":"2023","journal-title":"Front Synaptic Neurosci."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-025-06843-7","article-title":"Autism and dementia: a summative report from the 2nd international summit on intellectual disabilities and dementia","author":"Janicki","year":"2025","journal-title":"J. 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