Synaptic signaling associated with autism spectrum disorder (WP4539)

Synaptic signaling pathways associated with autism spectrum disorder (ASD). Changes in mTOR activation is 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 the 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 [https://en.wikipedia.org/wiki/Timothy_syndrome Timothy Syndrome]. Adapted from figure 1 from [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6085908/ Daghsni et al].

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