Serotonin Receptors as Therapeutic Targets for Autism Spectrum Disorder Treatment

Abstract

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by repetitive and stereotyped behaviors as well as difficulties with social interaction and communication. According to reports for prevalence rates of ASD, approximately 1~2% of children worldwide have been diagnosed with ASD. Although there are a couple of FDA (Food and Drug Administration)—approved drugs for ASD treatment such as aripiprazole and risperidone, they are efficient for alleviating aggression, hyperactivity, and self-injury but not the core symptoms. Serotonin (5-hydroxytryptamine, 5-HT) as a neurotransmitter plays a crucial role in the early neurodevelopmental stage. In particular, 5-HT has been known to regulate a variety of neurobiological processes including neurite outgrowth, dendritic spine morphology, shaping neuronal circuits, synaptic transmission, and synaptic plasticity. Given the roles of serotonergic systems, the 5-HT receptors (5-HTRs) become emerging as potential therapeutic targets in the ASD. In this review, we will focus on the recent development of small molecule modulators of 5-HTRs as therapeutic targets for the ASD treatment.

Identification of an Antagonist Targeting G Protein and β-Arrestin Signaling Pathways of 5-HT7R

“…Among 5-HTRs, 5-HT 7 R, the most recently identified subtype, exhibits expression within the central nervous system (CNS) regions, including thalamus, hippocampus, and cerebral cortex, as well as the peripheral nervous system (PNS) and the periphery tissues . Many studies have unveiled the significant roles of 5-HT 7 R in circadian rhythms, depression, and learning and memory. , Recent studies have highlighted the importance of the 5-HT 7 R in regulating behavioral symptoms of ASD. − Noteworthy findings indicate that a novel compound having an agonistic effect on 5-HT 7 R increases the duration of self-grooming, a repetitive behavior in ASD animal model, whereas a novel 5-HT 7 R antagonist decreases self-grooming behavior. , …”

“…ASD is a complex neurodevelopmental and neuropsychiatric disorder characterized by deficits in social communication and the manifestation of restricted/repetitive behaviors . ASD is intricately linked to impairments of neurogenesis, synaptic pruning, and synaptic plasticity. − ASD is often accompanied by secondary disorders such as seizure, depression, anxiety, and hyperactivity. − Diagnosing and treating ASD pose substantial challenges due to heterogeneity of symptoms, varying degrees of severity, comorbidity, and incomplete understanding of etiology. − ASD arises from a complex interplay of genetic and environmental factors, including epigenetic factors, gene polymorphism, viral infections, metabolic dysfunction, and dysfunction of neurotransmitters in the brain, such as serotonin, glutamate, and acetylcholine. , Studies of neurotransmitter dysfunction in the context of ASD have been consistently reported, and among these, the modulation of serotonin receptors has emerged as a factor associated with social deficits and repetitive behaviors. ,− …”

Deep Eutectic Solvents toward the Detection and Extraction of Neurotransmitters: An Emerging Paradigm for Biomedical Applications

“…In addition to the neurophysiological importance of NTs, these analytes can also be regarded as the most attractive drug candidates because of numerous biological activities involving therapeutic strategies. 11 Hence, the extraction of NTs from natural products has great importance. Most of the techniques involved in extracting NTs utilized conventional solvents, threatening the environment.…”

Extraction, Phytochemical profile and Neuroprotective Activity of Phyllanthus emblica Fruit Extract Against Sodium Valproate-Induced Postnatal Autism in BALB/c Mice via modulation of 5-HT1D, 5-HT2A, D2 receptor protein, oxidative stress and inflammatory biomarkers

“…In the initial stages of neurodevelopment, the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) is extremely important. In particular, 5-HT has been shown to control a number of neurobiological processes, such as synaptic transmission, synaptic plasticity, neurite outgrowth, and dendritic spine shape [9]. In autistic patients, repetitive behaviours may be related to hypersensitivity of the 5-HT1D receptors [10].…”