The molecular mechanisms underlying autism spectrum disorder (ASD) remain elusive, which limits the management options available in the clinic. Accumulating evidence indicates that the pineal gland/melatonin system is associated with the progression of ASD. Here, we review recent advances in our understanding of various mechanisms involving pathological process of ASD, including the abnormal breakdown of melatonin synthesis, the disturbance of intracellular MTNR1A signaling, the effects exerted by melatonin on hippocampal protein serine/threonine kinases, and immune dysregulation/inflammation during ASD. We believe that an in-depth understanding of the interplay between the action of the melatonin system and the onset of autism could promote the development of novel therapeutic strategies against ASD. We anticipate that targeting the neurotransmitters upstream pathway and downstream of melatonin in brain will lead to potential therapeutic treatment for ASD.
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