• Isabela Drehmer, Júlio Santos-Terra, Carmem Gottfried, and Iohanna Deckmann.
• Translational Research Group on Autism Spectrum Disorder - GETTEA, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil; National Institute of Science and Technology in Neuroimmunomodulation - INCT-NIM, Brazil; Autism Wellbeing and Research Development - AWARD - Initiative BR-UK-CA, Brazil; Psychiatry Molecular Laboratory, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil; Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Brazil; Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
• Neuroscience. 2024 Oct 30; 563: 334233-42.

AbstractAutism spectrum disorder (ASD) is a highly prevalent multifactorial disorder characterized by social deficits and stereotypies. Despite extensive research efforts, the etiology of ASD remains poorly understood. However, studies using preclinical models have identified the mechanistic target of rapamycin kinase (mTOR) signaling pathway as a key player in ASD-related features. This review examines genetic and environmental models of ASD, focusing on their association with the mTOR pathway. We organize findings on alterations within this pathway, providing insights about the potential mechanisms involved in the onset and maintenance of ASD symptoms. Our analysis highlights the central role of mTOR hyperactivation in disrupting autophagic processes, neural organization, and neurotransmitter pathways, which collectively contribute to ASD phenotypes. The review also discusses the therapeutic potential of mTOR pathway inhibitors, such as rapamycin, in mitigating ASD characteristics. These insights underscore the importance of the mTOR pathway as a target for future research and therapeutic intervention in ASD. This review innovates by bringing the convergence of disrupted mTOR signaling in preclinical models and clinical data associated with ASD.Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.

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