Changes in mTOR activation are believed to be a risk factor for ASD. mTOR is regulated by the TCS1/2 complex, and several signaling pathways upstream of TSC1/2 positively or negatively regulate this complex, including PI3K-AKT, Ras–ERK, LKB1–AMPK and Wnt–GSK3β pathways. The mTOR pathway is also regulated by brain‐derived neurotrophic factor (BDNF), which plays a key role in the development and the plasticity of the central nervous system and is considered a risk factor for ASD. Increased levels of BDNF concentration have been observed in the serum and brain of patients with ASD. mTOR is a key modulator of protein synthesis and thus blocks the activation of cell autophagy and promotes cell proliferation, growth, and differentiation. Proteasome activity is also affected by neuronal activity, via increased expression of UBE3A through transcription factor MEF2, which leads to the internalization of AMPA-R. Variations in the calcium channel CACNA1C are also associated with ASD and [Timothy syndrome](https://en.wikipedia.org/wiki/Timothy_syndrome). Adapted from figure 1 in [Daghsni et al](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6085908/). d9b Akt AMPK AMPK AMPK AMPK AMPK AMPK AMPK mGluR1 NMDAR NMDAR NMDAR NMDAR PI3K PI3K PI3K PI3K PSD95 Ras SYNGAP1 mTOR ErK HOMER1 Ras TRKB S6K1 NMDAR NF1 UBE3A BDNF PTEN Akt TSC1/ Ras NMDAR Rheb ARC CACNA1C CaMKII ErK NMDAR TSC2 Akt Raptor HOMER1 PI3K PI3K Rheb CaMKII autism spectrum disorder DOID:0060041 Disease 29934975 PubMed Autism throughout genetics: Perusal of the implication of ion channels. 2018 Brain Behav Daghsni M Rima M Fajloun Z Ronjat M Brusés JL M'rad R De Waard M mTOR signaling pathway PW:0000180 Pathway Ontology neuron CL:0000540 Cell Type