MedicalResearch.com: Interview with:
Anilkumar Pillai, Ph.D.
Associate Professor, Department of Psychiatry
Medical College of Georgia, Georgia Regents University
(Formerly Georgia Health Sciences University)
Medical Research: What are the main findings of the study?
Dr. Pillai: GABA receptors are responsible for binding GABA, the main inhibitory neurotransmitter in the human brain. Recent studies have indicated a potential role for alterations in GABAA receptors in the pathophysiology of Autism Spectrum Disorder (ASD). However, the mechanism of regulation of GABAA receptor in Autism Spectrum Disorder is not known. Our study shows that GABAA levels are altered at the protein level, but not at the mRNA level in the middle frontal gyrus of Autism Spectrum Disorder subjects. Our study also finds that Synoviolin 1 (SYVN1) plays a critical role as an E3 ligase in GABAAα1 degradation. SYVN1 has been previously determined to function as a removal system of inappropriately folded or unfolded proteins from the ER to the cytosol of the cell for degradation. Our study ultimately provides a mechanism for GABAAα1 deficits in Autism Spectrum Disorder subjects and possible new treatment strategies to reverse deficits seen in ASD and other related disorders.
Medical Research: Were any of the findings unexpected?
Dr. Pillai: Our findings were not unexpected as some studies have previously indicated alterations in GABAA signaling in Autism Spectrum Disorder. However, our studies are novel in that they provide a possible mechanism for these deficits. Our study provides a link between GABAergic deficits and ERAD-mediated proteasomal degradation, both of which have been previously implicated in Autism Spectrum Disorder.
Medical Research: What should clinicians and patients take away from your report?
Dr. Pillai: Autism is a widespread disorder affecting 1 in 68 children in America and has a 1% prevalence worldwide. This is a disorder that can be devastating to children and their families, but the cause of the disorder remains elusive. This study shows a new finding in inhibitory signaling in the brain, allowing for a better understanding of what is going on at the molecular level in the brains of individuals with Autism Spectrum Disorder. This study could have clinical implications in that use of a proteasome inhibitor or targeting specific elements of the ubiquitin proteasome system may allow for new treatment strategies in the deficits seen in Autism Spectrum Disorder and related disorders.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Pillai: The findings of this study may have functional implications in the pathophysiology of Autism Spectrum Disorder, but these findings need to be further tested in an appropriate animal model for ASD. Other literature in the field shows abnormalities in GABAergic function in other brain regions in patients with Autism Spectrum Disorder, so studying other brain regions from postmortem tissues of ASD subjects would be necessary to determine if our findings can provide a mechanism for some of these deficits as well.
Ubiquitin-proteasome dependent degradation of GABAAα1 in autism spectrum disorder Amanda Crider,Chirayu D Pandya,Diya Peter,Anthony O Ahmed,Anilkumar Pillai
Molecular Autism September 2014, 5:45,
Date: 01 Sep 2014