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Chemical Modulators for Targeting Autism Spectrum Disorders: From Bench to Clinic.

ABSTRACT: Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by diverse behavioral symptoms such as repetitive behaviors, social deficits, anxiety, hyperactivity, and irritability. Despite their increasing incidence, the specific pathological mechanisms of ASD are still unknown, and the degree and types of symptoms that vary from patient to patient make it difficult to develop drugs that target the core symptoms of ASD. Although various atypical antipsychotics and antidepressants have been applied to regulate ASD symptoms, these drugs can only alleviate the symptoms and do not target the major causes. Therefore, development of novel drugs targeting factors directly related to the onset of ASD is required. Among the various factors related to the onset of ASD, several chemical modulators to treat ASD, focused on serotonin (5-hydroxytryptamine, 5-HT) and glutamate receptors, microbial metabolites, and inflammatory cytokines, are explored in this study. In particular, we focus on the chemical drugs that have improved various aspects of ASD symptoms in animal models and in clinical trials for various ages of patients with ASD.

SUBMITTER: Lim S

PROVIDER: S-EPMC9414776 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Chemical Modulators for Targeting Autism Spectrum Disorders: From Bench to Clinic.

Lim Songhyun S Lee Sanghee S

Molecules (Basel, Switzerland) 20220810 16

Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by diverse behavioral symptoms such as repetitive behaviors, social deficits, anxiety, hyperactivity, and irritability. Despite their increasing incidence, the specific pathological mechanisms of ASD are still unknown, and the degree and types of symptoms that vary from patient to patient make it difficult to develop drugs that target the core symptoms of ASD. Although various atypical antipsychotics and antidepressan ...[more]

PMID: 36014340

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Project description:Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by delayed/abnormal language development, deficits in social interaction, repetitive behaviors and restricted interests. The heterogeneity in clinical presentation of ASD, likely due to different etiologies, complicates genetic/biological analyses of these disorders. DNA microarray analyses were conducted on 116 lymphoblastoid cell lines (LCL) from individuals with idiopathic autism who are divided into 3 phenotypic subgroups according to severity scores from the commonly used Autism Diagnostic Interview-Revised questionnaire and age-matched, nonautistic controls. Statistical analyses of gene expression data from control LCL against that of LCL from ASD probands identify genes for which expression levels are either quantitatively or qualitatively associated with phenotypic severity. Comparison of the significant differentially expressed genes from each subgroup relative to the control group reveals differentially expressed genes unique to each subgroup as well as genes in common across subgroups. Among the findings unique to the most severely affected ASD group are genes that regulate circadian rhythm, which has been shown to have multiple effects on neurological as well as metabolic functions commonly dysregulated in autism. Among the genes common to all 3 subgroups of ASD are 5 novel genes which appear to associate with androgen sensitivity, which may underlie the strong 4:1 bias towards affected males. Gene expression profiling of 116 LCL from autistic (87) and nonautistic (29) individuals were obtained using a custom-printed DNA microarray containing 39,936 elements (TIGR 40K Human array, GPL3427) and a reference design in which each sample was compared to the Stratagene Universal Human RNA standard. The 87 autistic samples were divided into phenotypic subgroups (language, mild, savant) on the basis of cluster analyses of scores from an autism diagnostic questionnaire, the Autism Diagnostic Interview-Revised instrument. Differentially expressed genes were determined for all autistic vs. control groups, as well as for each of 3 phenotypic ASD groups and controls.

Dataset Information

Chemical Modulators for Targeting Autism Spectrum Disorders: From Bench to Clinic.

Publications

Chemical Modulators for Targeting Autism Spectrum Disorders: From Bench to Clinic.

Similar Datasets

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