Exploring the multifactorial nature of autism through computational systems biology: Calcium and the Rho GTPase RAC1 under the spotlight

Fares Zeidán-Chuliá, José Luiz Rybarczyk-Filho, Alla B. Salmina, Ben Hur Neves De Oliveira, Mami Noda, José Cláudio F. Moreira

Research output: Contribution to journalReview article

33 Citations (Scopus)

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 (Ca2+) 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.

Original languageEnglish
Pages (from-to)364-383
Number of pages20
JournalNeuroMolecular Medicine
Volume15
Issue number2
DOIs
Publication statusPublished - Jun 1 2013

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Neurology
  • Cellular and Molecular Neuroscience

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