期刊
CHEMBIOCHEM
卷 21, 期 8, 页码 1052-1079出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201900573
关键词
aggregation; Alzheimer's disease; drug discovery; post-translational modifications; proteins
资金
- SwarnaJayanti Fellowship grant [DST/SJF/CSA-02/2015-2016]
- Department of Science and Technology (DST)
- Department of Biotechnology (DBT) [DBT/VN-HB-NC-SB/4515]
- Government of India, New Delhi, India
- Sheikh Saqr Laboratory (SSL)
- ICMS-JNCASR
- Alexander von Humboldt Foundation (Germany)
- JNCASR
The global burden of Alzheimer's disease (AD) is growing. Valiant efforts to develop clinical candidates for treatment have continuously met with failure. Currently available palliative treatments are temporary and there is a constant need to search for reliable disease pathways, biomarkers and drug targets for developing diagnostic and therapeutic tools to address the unmet medical needs of AD. Challenges in drug-discovery efforts raise further questions about the strategies of current conventional diagnosis; drug design; and understanding of disease pathways, biomarkers and targets. In this context, post-translational modifications (PTMs) regulate protein trafficking, function and degradation, and their in-depth study plays a significant role in the identification of novel biomarkers and drug targets. Aberrant PTMs of disease-relevant proteins could trigger pathological pathways, leading to disease progression. Advancements in proteomics enable the generation of patterns or signatures of such modifications, and thus, provide a versatile platform to develop biomarkers based on PTMs. In addition, understanding and targeting the aberrant PTMs of various proteins provide viable avenues for addressing AD drug-discovery challenges. This review highlights numerous PTMs of proteins relevant to AD and provides an overview of their adverse effects on the protein structure, function and aggregation propensity that contribute to the disease pathology. A critical discussion offers suggestions of methods to develop PTM signatures and interfere with aberrant PTMs to develop viable diagnostic and therapeutic interventions in AD.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据