Proteomic studies identified a single nucleotide polymorphism in glyoxalase I as autism susceptibility factor

Junaid, Mohammed A.; Kowal, Dagmar; Barua, Madhabi; Pullarkat, Premila S.; Brooks, Susan Sklower; Pullarkat, Raju K.

doi:10.1002/ajmg.a.30349

Cited by 144 publications

(137 citation statements)

References 47 publications

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“…The present study may also provide mechanistic insight into GLO1's proposed associations with other CNS diseases, such as autism (48,49), affective disorders (50,51), panic disorder (52), and schizophrenia (53). Human genome-wide association studies have identified an association between restless legs syndrome (RLS) and a haplotype containing GLO1 (54,55).…”

Section: Discussionmentioning

confidence: 89%

Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal

Distler¹,

Plant²,

Sokoloff³

et al. 2012

J. Clin. Invest.

135

214

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Glyoxalase 1 (Glo1) expression has previously been associated with anxiety in mice; however, its role in anxiety is controversial, and the underlying mechanism is unknown. Here, we demonstrate that GLO1 increases anxiety by reducing levels of methylglyoxal (MG), a GABA A receptor agonist. Mice overexpressing Glo1 on a Tg bacterial artificial chromosome displayed increased anxiety-like behavior and reduced brain MG concentrations. Treatment with low doses of MG reduced anxiety-like behavior, while higher doses caused locomotor depression, ataxia, and hypothermia, which are characteristic effects of GABA A receptor activation. Consistent with these data, we found that physiological concentrations of MG selectively activated GABA A receptors in primary neurons. These data indicate that GLO1 increases anxiety by reducing levels of MG, thereby decreasing GABA A receptor activation. More broadly, our findings potentially link metabolic state, neuronal inhibitory tone, and behavior. Finally, we demonstrated that pharmacological inhibition of GLO1 reduced anxiety, suggesting that GLO1 is a possible target for the treatment of anxiety disorders.

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Section: Discussionmentioning

confidence: 89%

Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal

Distler¹,

Plant²,

Sokoloff³

et al. 2012

J. Clin. Invest.

135

214

View full text Add to dashboard Cite

show abstract

“…43 Several recent studies have demonstrated the power of proteomics in understanding disease processes and elucidating the molecular defects associated with various conditions. 42,[44][45][46][47] Junaid et al 48 recently performed a proteomics study of autopsied brains of individuals with autism and found abnormalities that led to the identification of a single nucleotide polymorphism (SNP) in glyoxalase I, suggesting that it could be a susceptibility factor in autism. 48 The current cross-sectional study was designed to examine the proteome in serum from blood of children with autism (n = 69) ages four to six compared to typically developing children (n = 35) with similar age and gender distributions.…”

Section: Introductionmentioning

confidence: 99%

A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins

Corbett

Kantor²,

Schulman³

et al. 2006

Mol Psychiatry

167

113

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Modern methods that use systematic, quantitative and unbiased approaches are making it possible to discover proteins altered by a disease. To identify proteins that might be differentially expressed in autism, serum proteins from blood were subjected to trypsin digestion followed by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) on time-of-flight (TOF) instruments to identify differentially expressed peptides. Children with autism 4-6 years of age (n = 69) were compared to typically developing children (n = 35) with similar age and gender distributions. A total of 6348 peptide components were quantified. Of these, five peptide components corresponding to four known proteins had an effect size > 0.99 with a P < 0.05 and a Mascot identification score of 30 or greater for autism compared to controls. The four proteins were: Apolipoprotein (apo) B-100, Complement Factor H Related Protein (FHR1), Complement C1q and Fibronectin 1 (FN1). In addition, apo B-100 and apo A-IV were higher in children with high compared to low functioning autism. Apos are involved in the transport of lipids, cholesterol and vitamin E. The complement system is involved in the lysis and removal of infectious organisms in blood, and may be involved in cellular apoptosis in brain. Despite limitations of the study, including the low fold changes and variable detection rates for the peptide components, the data support possible differences of circulating proteins in autism, and should help stimulate the continued search for causes and treatments of autism by examining peripheral blood.

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“…Carriers of the Glyo-1 gene are susceptible to autism, and Glyo-1 variants are associated with autism [171][172]. These studies also found elevated levels of AGE receptors (RAGEs) and an accumulation of AGE the brains of people with autism.…”

Section: Other Rolementioning

confidence: 86%

The Role of Thiamine in Autism

Lương¹

2013

AJPN

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Autism spectrum disorders are a group of neuro-developmental conditions characterized by varying degrees of language impairment, including verbal and non-verbal communication, impaired social skill, and repetitive behaviors. In this paper, we review the evidence for an association between autism and thiamine. A relationship between thiamine status and the development of autism has been established, with thiamine supplementation exhibiting a beneficial clinical effect on children with autism. Thiamine may involve in autism via apoptotic factors (transcription factor p53, Bcl-2, and caspase-3), neurotransmitter systems (serotonin, acetylcholine, and glutamate), and oxidative stress (prostaglandins, cyclooxygenase-2, reactive oxygen species, nitric oxide synthase, the reduced form of nicotinamide adenine dinucleotide phosphate, and mitochondrial dysfunction). In addition, thiamine has also been implicated in autism via its effects on basic myelin protein, glycogen synthetase kinase-3β, alpha-1 antitrypsin, and glyoxalase 1. Thiamine may play a role in children with autism. Additional investigation of thiamine in children with autism is needed.

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Proteomic studies identified a single nucleotide polymorphism in glyoxalase I as autism susceptibility factor

Cited by 144 publications

References 47 publications

Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal

Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal

A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins

The Role of Thiamine in Autism

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