Palmitoylation-related gene ZDHHC22 as a potential diagnostic and immunomodulatory target in Alzheimer’s disease: insights from machine learning analyses and WGCNA

European journal of medical research, Journal Year: 2025, Volume and Issue: 30(1)

Published: Jan. 22, 2025

The mechanism of palmitoylation in the pathogenesis Alzheimer's disease (AD) remains unclear. This study retrieved AD data sets from GEO database to identify palmitoylation-associated genes (PRGs). applied WGCNA along with three machine learning algorithms—random forest, LASSO regression, and SVM–RFE—to further select key PRGs (KPRGs). diagnostic performance KPRGs was evaluated using Receiver Operating Characteristic (ROC) curve analysis. Immune cell infiltration analysis conducted assess correlations between immune types, a competing endogenous RNA (ceRNA) regulatory network constructed explore their potential mechanisms. 17 were identified sets, 7 showing increased expression 10 decreased expression. Through analyses, ZDHHC22 selected as KPRG. ROC demonstrated that had an area under value 0.659, indicating moderate potential. revealed significant associations several including naïve B cells, CD8 + T M1 macrophages. In addition, 25 miRNAs 55 lncRNAs predicted potentially target ZDHHC22, forming basis for lncRNA–miRNA–mRNA ceRNA network. is first use bioinformatics methods KPRG AD, highlighting its role diagnosis regulation. provides new insights into molecular mechanisms lays foundation future targeted therapeutic strategies.

Language: Английский

Protein palmitoylation: biological functions, disease, and therapeutic targets

MedComm, Journal Year: 2025, Volume and Issue: 6(3)

Published: Feb. 21, 2025

Abstract Protein palmitoylation, a reversible post‐translational lipid modification, is catalyzed by the ZDHHC family of palmitoyltransferases and reversed several acyl protein thioesterases, regulating localization, accumulation, secretion, function. Neurological disorders encompass spectrum diseases that affect both central peripheral nervous system. Recently, accumulating studies have revealed pathological associated with neurological diseases, such as β‐amyloid, α‐synuclein, Huntingtin, could undergo highlighting crucial roles palmitoylation in onset development diseases. However, few preclinical clinical trials focus on interventional strategies target palmitoylation. Here, we comprehensively reviewed emerging evidence role various summarized classification, processes, functions its impact stability, membrane protein–protein interaction, well signal transduction. Furthermore, also discussed potential targeting proteins elucidated their underlying pathogenic mechanisms Overall, an in‐depth understanding significances provide new avenues for investigating therapeutic approaches disorders.

Language: Английский

Microglia efferocytosis: an emerging mechanism for the resolution of neuroinflammation in Alzheimer’s disease

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: March 30, 2025

Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by significant neuroinflammatory responses. Microglia, the immune cells of central nervous system, play crucial role in pathophysiology AD. Recent studies have indicated that microglial efferocytosis an important mechanism for clearing apoptotic and cellular debris, facilitating resolution neuroinflammation. This review summarizes biological characteristics microglia mechanisms underlying efferocytosis, including factors signaling pathways regulate interactions between other influence this process, neuroinflammation Furthermore, we explore AD from three perspectives: its impact on clearance amyloid plaques, regulation neuroinflammation, effects neuroprotection. Finally, summarize current research status enhancing to alleviate improve AD, as well future challenges approach therapeutic strategy

Language: Английский