Therapeutic Implications and Regulations of Protein Post-translational Modifications in Parkinsons Disease.

IF 3.6 4区 医学 Q3 CELL BIOLOGY Cellular and Molecular Neurobiology Pub Date : 2024-07-03 DOI:10.1007/s10571-024-01471-8
Twinkle Mishra, Shareen Singh, Thakur Gurjeet Singh
{"title":"Therapeutic Implications and Regulations of Protein Post-translational Modifications in Parkinsons Disease.","authors":"Twinkle Mishra, Shareen Singh, Thakur Gurjeet Singh","doi":"10.1007/s10571-024-01471-8","DOIUrl":null,"url":null,"abstract":"<p><p>Parkinsons disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron loss and alpha-synuclein aggregation. This comprehensive review examines the intricate role of post-translational modifications (PTMs) in PD pathogenesis, focusing on DNA methylation, histone modifications, phosphorylation, SUMOylation, and ubiquitination. Targeted PTM modulation, particularly in key proteins like Parkin, DJ1, and PINK1, emerges as a promising therapeutic strategy for mitigating dopaminergic degeneration in PD. Dysregulated PTMs significantly contribute to the accumulation of toxic protein aggregates and dopaminergic neuronal dysfunction observed in PD. Targeting PTMs, including epigenetic strategies, addressing aberrant phosphorylation events, and modulating SUMOylation processes, provides potential avenues for intervention. The ubiquitin-proteasome system, governed by enzymes like Parkin and Nedd4, offers potential targets for clearing misfolded proteins and developing disease-modifying interventions. Compounds like ginkgolic acid, SUMO E1 enzyme inhibitors, and natural compounds like Indole-3-carbinol illustrate the feasibility of modulating PTMs for therapeutic purposes in PD. This review underscores the therapeutic potential of PTM-targeted interventions in modulating PD-related pathways, emphasizing the need for further research in this promising area of Parkinsons disease therapeutics.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11222187/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular and Molecular Neurobiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10571-024-01471-8","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Parkinsons disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron loss and alpha-synuclein aggregation. This comprehensive review examines the intricate role of post-translational modifications (PTMs) in PD pathogenesis, focusing on DNA methylation, histone modifications, phosphorylation, SUMOylation, and ubiquitination. Targeted PTM modulation, particularly in key proteins like Parkin, DJ1, and PINK1, emerges as a promising therapeutic strategy for mitigating dopaminergic degeneration in PD. Dysregulated PTMs significantly contribute to the accumulation of toxic protein aggregates and dopaminergic neuronal dysfunction observed in PD. Targeting PTMs, including epigenetic strategies, addressing aberrant phosphorylation events, and modulating SUMOylation processes, provides potential avenues for intervention. The ubiquitin-proteasome system, governed by enzymes like Parkin and Nedd4, offers potential targets for clearing misfolded proteins and developing disease-modifying interventions. Compounds like ginkgolic acid, SUMO E1 enzyme inhibitors, and natural compounds like Indole-3-carbinol illustrate the feasibility of modulating PTMs for therapeutic purposes in PD. This review underscores the therapeutic potential of PTM-targeted interventions in modulating PD-related pathways, emphasizing the need for further research in this promising area of Parkinsons disease therapeutics.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
帕金森氏症中蛋白质翻译后修饰的治疗意义和调节。
帕金森病(PD)是一种神经退行性疾病,以多巴胺能神经元缺失和α-突触核蛋白聚集为特征。本综述探讨了翻译后修饰(PTM)在帕金森病发病机制中的复杂作用,重点关注 DNA 甲基化、组蛋白修饰、磷酸化、SUMOylation 和泛素化。靶向 PTM 调节,尤其是对 Parkin、DJ1 和 PINK1 等关键蛋白的调节,已成为缓解帕金森病多巴胺能变性的一种很有前景的治疗策略。PTM 失调在很大程度上导致了帕金森病中毒性蛋白质聚集的积累和多巴胺能神经元功能障碍。靶向 PTMs(包括表观遗传学策略)、处理异常磷酸化事件和调节 SUMOylation 过程为干预提供了潜在的途径。由Parkin和Nedd4等酶支配的泛素-蛋白酶体系统为清除折叠错误的蛋白质和开发改善疾病的干预措施提供了潜在的靶点。银杏酸、SUMO E1酶抑制剂等化合物以及吲哚-3-甲醇等天然化合物说明了调节PTMs以治疗帕金森病的可行性。本综述强调了以 PTM 为靶点的干预措施在调节帕金森病相关通路方面的治疗潜力,并强调了在这一前景广阔的帕金森病治疗领域开展进一步研究的必要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
7.70
自引率
0.00%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Cellular and Molecular Neurobiology publishes original research concerned with the analysis of neuronal and brain function at the cellular and subcellular levels. The journal offers timely, peer-reviewed articles that describe anatomic, genetic, physiologic, pharmacologic, and biochemical approaches to the study of neuronal function and the analysis of elementary mechanisms. Studies are presented on isolated mammalian tissues and intact animals, with investigations aimed at the molecular mechanisms or neuronal responses at the level of single cells. Cellular and Molecular Neurobiology also presents studies of the effects of neurons on other organ systems, such as analysis of the electrical or biochemical response to neurotransmitters or neurohormones on smooth muscle or gland cells.
期刊最新文献
Pesticide Exposure and Its Association with Parkinson's Disease: A Case-Control Analysis. Cognitive Impact of Neurotropic Pathogens: Investigating Molecular Mimicry through Computational Methods. Genetic Variability in Oxidative Stress, Inflammatory, and Neurodevelopmental Pathways: Impact on the Susceptibility and Course of Spinal Muscular Atrophy. Metformin Mitigates Trimethyltin-Induced Cognition Impairment and Hippocampal Neurodegeneration. Can Environmental Enrichment Modulate Epigenetic Processes in the Central Nervous System Under Adverse Environmental Conditions? A Systematic Review.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1