A pilot proteomic study of protein markers in autism spectrum disorder

Abstract

Autism spectrum disorder (ASD) diagnosis is increasing, with 1/88 children believed to be affected by the disorder, with a most recent survey suggesting numbers as high as 1/50. Treatment and understanding of ASD causes is a pressing health concern. ASD protein biomarkers may provide clues about ASD cause. Protein biomarkers for ASDs could be used for ASD diagnosis, subtyping, treatment monitoring, and identifying therapeutic targets. Here, we analyzed the sera from seven children with ASD and seven matched controls using Tricine gel electrophoresis (Tricine-PAGE) and LC-MS/MS. Overall, we found increased levels of apolipoproteins ApoA1 and ApoA4, involved in cholesterol metabolism and of serum paraoxanase/arylesterase 1, involved in preventing oxidative damage, in the sera of children with ASD, compared with their matched controls. All three proteins are predicted to interact with each other and are parts of high-density lipoproteins. Further studies are needed to validate these findings in larger subject numbers.

Environmental Influences on Biochemistry in Autism Spectrum Disorder

“…The presence of autism in SLOS supports the idea that lipid associated pathways may be disrupted in ASD [17,23]. There has also been evidence of increased levels of serum paraoxanase/arylesterase 1 (PON1), which is involved in toxin metabolism and detoxification, and could help prevent oxidative stress [13]. Interestingly, PON1 is a component of high density lipoprotein (HDL) [24], further attesting to possible lipid disturbances in ASD.…”

“…PON1 is a marker for organophosphate pesticide exposure [27] and as mentioned, may be elevated in individuals with ASD [13]. PON1 enzyme activity has been observed to be low in some individuals with autism [28,29] and gene mutations in PON1 are associated with autism in the United States (where there is more pesticide use) but not in Italy [27].…”

“…Two hypothetical dysregulated systems in individuals with ASD include cholesterol and associated molecules and the immune system. Studies have shown increased levels of two apolipoproteins, apoA1 and apoA4, responsible for lipid transport, in people with ASD compared to matched controls [13,21]. Autism is a common comorbidity for Smith-Lemli Opitz Syndrome (SLOS).…”

“…Numerous methods have been employed to try to determine ASD susceptibility genes which include chromosomal studies, linkage studies and gene association studies [8]. Candidate autism susceptibility genes have been identified at multiple loci, most consistently on chromosomes 2q, 7q, 15q [11][12][13], 17q and 16p with the most consistent positive results coming from 7q [18,19]. Although the numerous genetic studies conducted on ASD have been successful in identifying potential chromosomal abnormalities, truncations and missense mutations, the detection of the specific genetic variants responsible for ASD have been mostly elusive, likely due to the high genetic complexity and probable heterogeneity of the disorder [8].…”

Proteomic analysis of mucopolysaccharidosis I mouse brain with two-dimensional polyacrylamide gel electrophoresis

“…Picked spots were excised and subjected to in-gel tryptic digestion and peptide extraction for protein identification by nanoLC-MS/MS analysis, as described before (19). Briefly, spots were washed in HPLC grade water, 50 mM ammonium bicarbonate (ABC), 50% acetonitrile (ACN)/50% ABC for each 15 minutes under moderate shaking at room temperature.…”