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基于功能能力的亨廷顿舞蹈病蛋白质组学初步分析

A Pilot Proteomic Analysis of Huntington's Disease by Functional Capacity.

作者信息

McGarry Andrew, Moaddel Ruin

机构信息

Cooper University Healthcare at Rowan University, Camden, NJ 08103, USA.

Biomedical Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.

出版信息

Brain Sci. 2025 Jan 16;15(1):76. doi: 10.3390/brainsci15010076.

Abstract

The molecular biology of Huntington's Disease (HD) has grown substantially, with pathological considerations extending to genetic modifiers, epigenetic changes, transcriptomics, the proteome, and the metabolome. The metabolome and proteome are especially intriguing in that they most directly reflect the functional state of the cellular environment, which may involve some combination of pathology as well as compensation. We assessed CSF proteomics from eight participants by their functional severity (TFC range 3-13), with 47 proteins having a minimum r-value of 0.7 and nominal -values < 0.05. : Our exploratory data reveal correlations between progression and several processes including inflammation, ECM homeostasis and NAD metabolism. Consistently identified targets that correlate with phenotype or progression may have value, if validated, as enrichment tools in clinical trials and potentially as markers of therapeutic response.

摘要

亨廷顿舞蹈症(HD)的分子生物学有了长足发展,病理考量已扩展至基因修饰因子、表观遗传变化、转录组学、蛋白质组和代谢组。代谢组和蛋白质组尤其引人关注,因为它们最直接地反映了细胞环境的功能状态,这可能涉及病理以及代偿的某种组合。我们根据功能严重程度(统一功能评定量表范围为3 - 13)评估了8名参与者的脑脊液蛋白质组学,其中47种蛋白质的最小r值为0.7,名义p值<0.05。我们的探索性数据揭示了疾病进展与包括炎症、细胞外基质稳态和NAD代谢在内的多个过程之间的相关性。如果得到验证,与表型或疾病进展相关的一致鉴定出的靶点可能作为临床试验中的富集工具具有价值,并有可能作为治疗反应的标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24d5/11764106/5f23f7f946d1/brainsci-15-00076-g001.jpg

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