Signalling Dysregulation of the PI3K/AKT/mTOR Pathway and Its Links to Autophagy and Mitochondrial Function in Autism Spectrum Disorder

Siampakou, Evangelina (2025) Signalling Dysregulation of the PI3K/AKT/mTOR Pathway and Its Links to Autophagy and Mitochondrial Function in Autism Spectrum Disorder. Master's Thesis / Essay, Biomedical Sciences.

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Abstract

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition defined by atypical communication and social interaction, along with restricted and repetitive behaviours, the aetiology of which involves variation in brain connectivity and synaptic signalling. The mechanistic target of rapamycin (mTOR) is a serine/threonine kinase crucial for regulating neuronal growth, circuit formation, and synaptic plasticity. Aberrant mTOR signalling is associated with multiple neurological disorders, including ASD. This essay aims to delineate the mechanistic role of the PI3K/AKT/mTOR pathway in ASD neuropathology, specifically focusing on metabolic regulation. Preclinically, aberrant mTOR hyperactivation is established as a shared molecular feature in multiple syndromic ASD models (such as TSC, PHTS and FXS), consistently correlating with defective neuronal development and atypical behavioural phenotypes. As a consequence of this hyperactivation, impaired autophagy is linked to suppressed and ineffective synaptic pruning during early brain development, which alters synaptic plasticity. Furthermore, neurons are rendered metabolically vulnerable by depriving the energy supply necessary for synaptic function while simultaneously inducing mitochondrial oxidative damage and suppressing quality control mechanisms like mitophagy. By focusing on these metabolic mechanisms, this essay aims to assess molecular processes underlying ASD and highlight potential targets for therapeutic intervention.

Item Type:	Thesis (Master's Thesis / Essay)
Supervisor name:	Drion, C.M.
Degree programme:	Biomedical Sciences
Thesis type:	Master's Thesis / Essay
Language:	English
Date Deposited:	17 Dec 2025 13:25
Last Modified:	17 Dec 2025 13:25
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/37176

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