Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition.

For over a decade, folic acid (FA) supplementation has been widely prescribed to pregnant women to prevent neural tube closure defects in newborns. Although neural tube closure occurs within the first trimester, high doses of FA are given throughout pregnancy, the physiological consequences of which are unknown. FA can cause epigenetic modification of the cytosine residues in the CpG dinucleotide, thereby affecting gene expression.

Glyoxalase I polymorphism rs2736654 causing the Ala111Glu substitution modulates enzyme activity--implications for autism.

Autism is a pervasive, heterogeneous, neurodevelopmental disability characterized by impairments in verbal communications, reciprocal social interactions, and restricted repetitive stereotyped behaviors. Evidence suggests the involvement of multiple genetic factors in the etiology of autism, and extensive genome-wide association studies have revealed several candidate genes that bear single nucleotide polymorphisms (SNPs) in non-coding and coding regions. We have shown that a non-conservative, non-synonymous SNP in the glyoxalase I gene, GLOI, may be an autism susceptibility factor.

A critical tryptophan and Ca2+ in activation and catalysis of TPPI, the enzyme deficient in classic late-infantile neuronal ceroid lipofuscinosis.

Background: Tripeptidyl aminopeptidase I (TPPI) is a crucial lysosomal enzyme that is deficient in the fatal neurodegenerative disorder called classic late-infantile neuronal ceroid lipofuscinosis (LINCL). It is involved in the catabolism of proteins in the lysosomes. Recent X-ray crystallographic studies have provided insights into the structural/functional aspects of TPPI catalysis, and indicated presence of an octahedrally coordinated Ca(2+).

Differential expression of small heat shock protein 27 (Hsp27) in Ataxia telangiectasia brains.

Ataxia telangiectasia (A-T) is a progressive neurodegenerative disorder caused by disruption of the gene, ataxia telangiectasia mutated (ATM). Present study was aimed at identifying proteins that are present in abnormal levels in A-T brain that may identify alternative targets for therapeutic interventions. Proteomic and Western blot analysis have shown massive expression of the small heat shock protein 27 (Hsp27) in frontal cortices of A-T brains compared to negligible levels in controls.

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

Autism is a neurodevelopmental disability characterized by deficits in verbal communications, impairments in social interactions, and repetitive behaviors. Several studies have indicated strong involvement of multigenic components in the etiology of autism. Linkage analyses and candidate gene search approaches so far have not identified any reliable susceptibility genes.