Ann N Y Acad Sci. 2025 Nov 24. doi: 10.1111/nyas.70144. Online ahead of print.
ABSTRACT
Various cellular processes, such as DNA repair and signal transduction, are regulated through ubiquitination and deubiquitination. Dysregulation of ubiquitination cascade enzymes and deubiquitinating enzymes leads to various diseases. Among them, deubiquitinating enzymes have been shown to be closely associated with cancer, cardiovascular disease, and metabolic diseases. Recent studies have found that deubiquitinating enzymes play an important role in controlling neuronal fate, synaptic development, and maintaining normal nervous system function. USP10, a member of the deubiquitinating enzyme family, regulates the progression of various diseases by acting on different substrates and modulating their functions. USP10 has been shown to regulate neurological diseases by mediating pathways such as immune response, oxidative stress, and apoptosis. This review provides a comprehensive overview of the molecular structure of USP10, identifies its substrate-binding sites, and summarizes its biological functions, particularly in relation to neurological diseases, including Alzheimer's disease, Parkinson's disease, glioblastoma, and ischemic stroke. USP10 promotes pathological progression in Alzheimer's disease and glioblastoma on the one hand, and exerts protective effects in Parkinson's disease and ischemic stroke on the other. Additionally, we summarize recent progress in the development and application of USP10 modulators and potential therapeutic strategies targeting USP10 in neurological disorders.
PMID:41284210 | DOI:10.1111/nyas.70144