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GA I patients usually present progressive cortical leukodystrophy and frequently develop acute striatal degeneration during encephalopathic crises during the first three years of life. The pathophysiology of the neurodegeneration observed in GA I is still partly known, although the development of the genetic mice model of GA I (<jats:italic>Gcdh<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic>) has contributed to clarify potential underlying mechanisms involved in brain damage in this disease. In this review we will summarize the knowledge acquired from studies using this animal model indicating that disruption of redox homeostasis, glutamatergic neurotransmission and bioenergetics, as well as vascular alterations, blood\u2010brain barrier breakage and altered myelination underlie the cortical and striatum abnormalities and white matter changes observed in GA I patients. Elucidation of these pathomechanisms potentially offers new standpoints for the development of novel therapeutic strategies for this disease.<\/jats:p>","DOI":"10.1016\/j.ijdevneu.2019.05.005","type":"journal-article","created":{"date-parts":[[2019,5,21]],"date-time":"2019-05-21T15:59:20Z","timestamp":1558454360000},"page":"215-221","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Pathogenesis of brain damage in glutaric acidemia type I: Lessons from the genetic mice model"],"prefix":"10.1002","volume":"78","author":[{"given":"Moacir","family":"Wajner","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Ci\u00eancias Biol\u00f3gicas: Bioqu\u00edmica Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade Universidade Federal do Rio Grande do Sul Porto Alegre RS Brazil"},{"name":"Departamento de Bioqu\u00edmica Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade Universidade 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