Identification and immune characteristics of molecular subtypes related to protein glycosylation in Alzheimer’s disease

Abstract

BackgroundProtein glycosylation has been confirmed to be involved in the pathological mechanisms of Alzheimer’s disease (AD); however, there is still a lack of systematic analysis of the immune processes mediated by protein glycosylation-related genes (PGRGs) in AD.Materials and methodsTranscriptomic data of AD patients were obtained from the Gene Expression Omnibus database and divided into training and verification datasets. The core PGRGs of the training set were identified by weighted gene co-expression network analysis, and protein glycosylation-related subtypes in AD were identified based on k-means unsupervised clustering. Protein glycosylation scores and neuroinflammatory levels of different subtypes were compared, and functional enrichment analysis and drug prediction were performed based on the differentially expressed genes (DEGs) between the subtypes. A random forest model was used to select important DEGs as diagnostic markers between subtypes, and a line chart model was constructed and verified in other datasets. We evaluated the differences in immune cell infiltration between the subtypes through the single-sample gene set enrichment analysis, analyzed the correlation between core diagnostic markers and immune cells, and explored the expression regulation network of the core diagnostic markers.ResultsEight core PGRGs were differentially expressed between the training set and control samples. AD was divided into two subtypes with significantly different biological processes, such as vesicle-mediated transport in synapses and neuroactive ligand-receptor interactions. The high protein glycosylation subtype had a higher level of neuroinflammation. Riluzole and sulfasalazine were found to have potential clinical value in this subtype. A reliable construction line chart model was constructed based on nine diagnostic markers, and SERPINA3 was identified as the core diagnostic marker. There were significant differences in immune cell infiltration between the two subtypes. SERPINA3 was found to be closely related to immune cells, and the expression of SERPINA3 in AD was found to be regulated by a competing endogenous RNA network that involves eight long non-coding RNAs and seven microRNAs.ConclusionProtein glycosylation and its corresponding immune process play an important role in the occurrence and development of AD. Understanding the role of PGRGs in AD may provide a new potential therapeutic target for AD.

Mettl1-mediated internal m7G methylation of Sptbn2 mRNA elicits neurogenesis and anti-alzheimer’s disease

“…This correlation is clearly confirmed by our findings that ectopic expression and depletion of Mettl1 mediates adult hippocampal neurogenesis in vitro and in vivo, and improves cognitive deficits of AD, indicating that Mettl1-mediated internal m 7 G dysregulation contributes to the pathophysiology of AD. Recent research discovers the biological significance of m 7 G methylation modification in AD and develops potential predictive models to assess the risk of m 7 G subtypes and the pathological outcomes of patients with AD [29]. However, more work about the direct interplay between the internal m 7 G and AD still awaits elucidation.…”

Disulfidptosis decoded: a journey through cell death mysteries, regulatory networks, disease paradigms and future directions

“…Lung Cancer: G6PD [32]; OGFRP1 [33] Reproductive System Breast Cancer: CD80, CD276 [34]; DNUFS1, LRPPRC, SLC7A11 [35] Neurodeenerative diseases MYH9, IQGAP1, ACTN4, DSTN, ACTB, MYL6, GYS1 [45] Metabolic diseases TRXR1, NFATC1 [46]…”

“…A study identified seven genes associated with disulfidptosis (MYH9, IQGAP1, ACTN4, DSTN, ACTB, MYL6, and GYS1). These genes can not only accurately assess AD subtypes, but also diagnose AD patients, providing new insights into the disease's potential pathogenesis and treatment strategies [45].…”

New insight into protein glycosylation in the development of Alzheimer’s disease

“…The glycosylation pattern of some other proteins such as TREM2 and reelin that play a role in cell signaling is also altered [ 30 , 37 ]. It has also been shown that protein glycosylation can alter immune processes, induce inflammatory responses in the brain, and affect the development of AD [ 38 ]. Glycomics studies, on the other hand, have quantitatively demonstrated changes in the frequency of overall protein glycosylation in AD brains as well as specific alterations in the glycosylation patterns of a large number of proteins and mapped glycoprotein profiles in different brain regions [ 32 , 39 , 40 ].…”