title: Exploring the multifactorial nature of autism through computational systems biology: calcium and the Rho GTPase RAC1 under the spotlight.
abstract: Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication accompanied with repetitive behavioral patterns and unusual stereotyped interests. Autism is considered a highly heterogeneous disorder with diverse putative causes and associated factors giving rise to variable ranges of symptomatology. Incidence seems to be increasing with time, while the underlying pathophysiological mechanisms remain virtually uncharacterized (or unknown). By systematic review of the literature and a systems biology approach, our aims were to examine the multifactorial nature of autism with its broad range of severity, to ascertain the predominant biological processes, cellular components, and molecular functions integral to the disorder, and finally, to elucidate the most central contributions (genetic and/or environmental) in silico. With this goal, we developed an integrative network model for gene-environment interactions (GENVI model) where calcium (Ca(2+)) was shown to be its most relevant node. Moreover, considering the present data from our systems biology approach together with the results from the differential gene expression analysis of cerebellar samples from autistic patients, we believe that RAC1, in particular, and the RHO family of GTPases, in general, could play a critical role in the neuropathological events associated with autism.
authors: Center of Oxidative Stress Research, Department of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. fzchulia.biomed@gmail.com
authors: Fares
authors: F
authors: Zeidán-Chuliá
authors: José Luiz
authors: JL
authors: Rybarczyk-Filho
authors: Alla B
authors: AB
authors: Salmina
authors: Ben-Hur Neves
authors: BH
authors: de Oliveira
authors: Mami
authors: M
authors: Noda
authors: José Cláudio F
authors: JC
authors: Moreira
mesh_terms: D001321:Autistic Disorder / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D001706:Biopsy; D002118:Calcium / Q000502:physiology; D002450:Cell Communication; D002490:Central Nervous System / Q000196:embryology / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology; D016208:Databases, Factual; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D059647:Gene-Environment Interaction; D006801:Humans; D046228:Microarray Analysis; D008957:Models, Genetic; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology; D049490:Systems Biology; D020830:rac1 GTP-Binding Protein / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000502:physiology
chemical_list: D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; C107953:RAC1 protein, human; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D002118:Calcium