Anti-GSK3B monoclonal antibody

Glycogen synthase kinase-3B (GSK-3B) is thought to be involved in numerous neuronal functions and is implicated in the pathophysiology of schizophrenia. Interestingly, a functional polymorphism, rs3755557, in the GSK3B promoter region has been consistently reported to be a risk factor for schizophrenia in southwestern and northwestern Han Chinese individuals. In this study, we carried out a comprehensive analysis of the association of the rs3755557 polymorphism within GSK3B and schizophrenia in Han Chinese individuals. We recruited 782 patients with schizophrenia and 807 healthy controls from eastern China. In total, 143 drug-naive patients with first-episode schizophrenia were enrolled for the evaluation of clinical features. We did not observe significant differences in genotype or allele distribution of the rs3755557 polymorphism between the schizophrenia and control groups in eastern Chinese individuals. After pooling these data of 2188 subjects with schizophrenia and 2885 healthy controls, we observed a significant difference in the A allele distribution of the rs3755557 polymorphism between schizophrenia patients and controls (Z = 4.13 P < 0.01). We further examined the relationship between the rs3755557 polymorphism and the clinical features of schizophrenia by comparing scores of the The Positive and Negative Syndrome Scale (PANSS) and The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) with the genotypes of the rs3755557 polymorphism. There were significant differences in the scores of RBANS attention, delayed memory and total scores between the patients with the A allele and those without the A allele (P = 0.03, 0.01 and 0.01 after Bonferroni correction, respectively). Our eQTL analysis showed a significant association between the rs3755557 polymorphism and GSK3B expression in the hippocampus (P = 0.027). Our findings indicated that the rs3755557 polymorphism may confer susceptibility to schizophrenia and cognitive dysfunction in Han Chinese individuals.

Alzheimer's disease (AD) is genetically complex with multifactorial etiology. Here, we aim to identify the potential viral pathogens leading to aberrant inflammatory and oxidative stress response in AD along with potential drug candidates using systems biology approach. We retrieved protein interactions of amyloid precursor protein (APP) and tau protein (MAPT) from NCBI and genes for oxidative stress from NetAge, for inflammation from NetAge and InnateDB databases. Genes implicated in aging were retrieved from GenAge database and two GEO expression datasets. These genes were individually used to create protein-protein interaction network using STRING database (score >= 0.7). The interactions of candidate genes with known viruses were mapped using virhostnet v2.0 database. Drug molecules targeting candidate genes were retrieved using the Drug-Gene Interaction Database (DGIdb). Data mining resulted in 2095 APP, 116 MAPT, 214 oxidative stress, 1269 inflammatory genes. After STRING PPIN analysis, 404 APP, 109 MAPT, 204 oxidative stress and 1014 inflammation related high confidence proteins were identified. The overlap among all datasets yielded eight common markers (AKT1, GSK3B, APP, APOE, EGFR, PIN1, CASP8 and SNCA). These genes showed association with hepatitis C virus (HCV), Epstein-Barr virus (EBV), human herpes virus 8 and Human papillomavirus (HPV). Further, screening of drugs targeting candidate genes, and possessing anti-inflammatory property, antiviral activity along with a suggested role in AD pathophysiology yielded 12 potential drug candidates. Our study demonstrated the role of viral etiology in AD pathogenesis by elucidating interaction of oxidative stress and inflammation causing candidate genes with common viruses along with the identification of potential AD drug candidates.