Anti-GSK3B monoclonal antibody

Objective: Although it is well known that GSK3 participates in the proliferation and survival of various tumor cells, its role in diseases of the central nervous system has been sparsely documented. In the past few years, studies regarding the relationship between GSK3 rs334558 T>C and rs6438552 C>T polymorphisms and Alzheimer disease (AD) risk have yielded contradictory results. As such, this meta-analysis seeks to satisfy the need to further investigate this relationship. Methods: In this research, published studies regarding the association of GSK3 rs6438552 and rs334558 mutation with AD risk was systematically assessed. Studies were retrieved from MEDLINE, Science Citation Index, the Cochrane Library, PubMed, Embase, CINAHL, Current Contents Index, Chinese Biomedical, Chinese Journal Full-Text, and Weipu Journal. Pooled odds ratios and 95% confidence intervals were calculated for allele contrast and homozygous, heterozygous, dominant, and recessive genetic model comparisons. Results: It was found that GSK3 rs334558 T>C and rs6438552 C>T polymorphisms were correlated with susceptibility to AD under 4 genetic models (all P < .05). In country-stratified subgroups, the results showed increased risk of developing AD in rs334558 T>C polymorphism among Chinese and Spain populations in majority groups. GSK3 rs6438552 C>T polymorphism was correlated with increased the risk of developing AD only in Australian populations. Conclusion: Our findings suggest that there exists a significant association between GSK3 rs334558 T>C polymorphism and increased susceptibility of AD. Moreover, future updated studies with stratified case-control population are warranted for validation studies.

The consequences of two-week hindlimb suspension (HS) on skeletal muscle atrophy were investigated in balanced diet-fed Fat-1 transgenic and C57BL/6 wild-type mice. Body composition and gastrocnemius fatty acid composition were measured. Skeletal muscle force, cross-sectional area (CSA), and signaling pathways associated with protein synthesis (protein kinase B, Akt; ribosomal protein S6, S6, eukaryotic translation initiation factor 4E-binding protein 1, 4EBP1; glycogen synthase kinase3-beta, GSK3-beta; and extracellular-signal-regulated kinases 1/2, ERK 1/2) and protein degradation (atrophy gene-1/muscle atrophy F-box, atrogin-1/MAFbx and muscle RING finger 1, MuRF1) were evaluated in the soleus muscle. HS decreased soleus muscle wet and dry weights (by 43% and 26%, respectively), muscle isotonic and tetanic force (by 29% and 18%, respectively), CSA of the soleus muscle (by 36%), and soleus muscle fibers (by 45%). Fat-1 transgenic mice had a decrease in the omega-6/omega-3 polyunsaturated fatty acids (PUFAs) ratio as compared with C57BL/6 wild-type mice (56%, p < 0.001). Fat-1 mice had lower soleus muscle dry mass loss (by 10%) and preserved absolute isotonic force (by 17%) and CSA of the soleus muscle (by 28%) after HS as compared with C57BL/6 wild-type mice. p-GSK3B/GSK3B ratio was increased (by 70%) and MuRF-1 content decreased (by 50%) in the soleus muscle of Fat-1 mice after HS. Balanced diet-fed Fat-1 mice are able to preserve in part the soleus muscle mass, absolute isotonic force and CSA of the soleus muscle in a disuse condition.