Proteomics Research Revealed the Latest Molecular Mechanisms of Alzheimer's Disease

Delayed and unscheduled Alzheimer's disease accounts for 99% of all such diseases, and it is associated with a variety of pathogenic factors and pathological mechanisms. One of them is a post-translational modification process of proteins called "O-linked beta-N acetylglucosamine modification" or "O-GlcNAc".

The low content and easily decomposable properties of O-GlcNAc make it difficult to study this type of protein modification, and it is also difficult for scientists to quantitatively study O-GlcNAc on a large scale.

According to an article published in the Journal of Pathology, researchers used a new approach to integrated proteomics to study this type of protein modification in detail. The author of the article is Cheng-Xin Gong from the City University of New York and Sheng Wang from the Pacific Northwest National Laboratory.

This study systematically quantified proteomic analysis of the characteristics of O-GlcNAc modification in the brain. They compared the levels of O-GlcNAc modification of more than 1000 peptides in multiple samples by performing multiple isotope labeling and drawing on previous study. This result provides new ideas for studying the pathogenesis of Alzheimer's disease. In addition, this high-throughput approach can be extended to other types of protein modification studies (eg, phosphorylation, etc.) to help reveal the intrinsic link between O-GlcNAc and the onset of Alzheimer's disease.

This study systematically quantified proteomic analysis of the characteristics of O-GlcNAc modification in the brain. They compared the levels of O-GlcNAc modification of more than 1000 peptides in multiple samples by performing multiple isotope labeling and drawing on previous study. This result provides new ideas for studying the pathogenesis of Alzheimer's disease. In addition, this high-throughput approach can be extended to other types of protein modification studies (eg, phosphorylation, etc.) to help reveal the intrinsic link between O-GlcNAc and the onset of Alzheimer's disease.

Many proteins in cells are affected by O-GlcNAc modification, which is important for regulating cellular activities such as metabolism, signaling, and transcription. Recently, researchers have found a link between this modification process and the onset of Alzheimer's disease, so a systematic analysis of O-GlcNAc modification in the brain helps to better understand the pathogenesis of Alzheimer's disease

Recent advances in some proteomics technologies have made research into O-GlcNAc modification feasible. This article shows that the integrated protein pipeline approach can focus on these advantages, namely the ability to combine isotope random labeling techniques with efficient isobaric enrichment strategies.

In this study, the authors analyzed brain samples from 10 healthy individuals and 10 Alzheimer's patients. Further, they found that there were 1,850 polypeptides with O-GlcNAc modification characteristics in frozen brain tissue samples, which were derived from 530 proteins. It is conservatively estimated that at least 1094 peptides are reliable. Of these proteins, 131 have abnormalities in the brains of Alzheimer's patients.

This study is currently the most systematic work on proteomics for the modification of brain O-GlcNAc. In conclusion, the authors hope that these results will help further study the relationship between protein phosphorylation and O-GlcNAc modification, and ultimately find ways to treat patients with Alzheimer's disease.

Prime Jones is a senior researcher from MtoZ Biolabs. She is specialized in the field of proteomics study.