Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autism spectrum disorders (ASD) are diagnosed on the basis of three behavioral features namely deficits in social communication, absence or delay in language, and stereotypy. The susceptibility genes to ASD remain largely unknown, but two major pathways are emerging. Mutations in TSC1/TSC2, NF1, or PTEN activate the mTOR/PI3K pathway and lead to syndromic ASD with tuberous sclerosis, neurofibromatosis, or macrocephaly. Mutations in NLGN3/4, SHANK3, or NRXN1 alter synaptic function and lead to mental retardation, typical autism, or Asperger syndrome. The mTOR/PI3K pathway is associated with abnormal cellular/synaptic growth rate, whereas the NRXN-NLGN-SHANK pathway is associated with synaptogenesis and imbalance between excitatory and inhibitory currents. Taken together, these data strongly suggest that abnormal synaptic homeostasis represent a risk factor to ASD.
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PMID:A synaptic trek to autism. 1954 94

Autism spectrum disorder (ASD) is a complex heterogeneous consortium of pervasive development disorders (PDD) which ranges from atypical autism, autism, and Asperger syndrome affecting brain in the developmental stage. This debilitating neurodevelopmental disorder results in both core as well as associated symptoms. Core symptoms observed in autistic patients are lack of social interaction, pervasive, stereotyped, and restricted behavior while the associated symptoms include irritability, anxiety, aggression, and several comorbid disorders.ASD is a polygenic disorder and is multifactorial in origin. Copy number variations (CNVs) of several genes that regulate the synaptogenesis and signaling pathways are one of the major factors responsible for the pathogenesis of autism. The complex integration of various CNVs cause mutations in the genes which code for molecules involved in cell adhesion, voltage-gated ion-channels, scaffolding proteins as well as signaling pathways (PTEN and mTOR pathways). These mutated genes are responsible for affecting synaptic transmission by causing plasticity dysfunction responsible, in turn, for the expression of ASD.Epigenetic modifications affecting DNA transcription and various pre-natal and post-natal exposure to a variety of environmental factors are also precipitating factors for the occurrence of ASD. All of these together cause dysregulation of glutamatergic signaling as well as imbalance in excitatory: inhibitory pathways resulting in glial cell activation and release of inflammatory mediators responsible for the aberrant social behavior which is observed in autistic patients.In this chapter we review and provide insight into the intricate integration of various genetic, epigenetic, and environmental factors which play a major role in the pathogenesis of this disorder and the mechanistic approach behind this integration.
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PMID:Neuropsychopathology of Autism Spectrum Disorder: Complex Interplay of Genetic, Epigenetic, and Environmental Factors. 3200 58