Targeting amyloid proteins for clinical diagnosis of neurodegenerative diseases
作者机构：Bio-X InstitutesKey Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education)Shanghai Jiao Tong UniversityShanghai 200030China School of Life Sciences and BiotechnologyShanghai Jiao Tong UniversityShanghai 200030China Interdisciplinary Research Center on Biology and ChemistryShanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 201210China University of the Chinese Academy of SciencesBeijing 100049China State Key Laboratory of Bio-Organic and Natural Products ChemistryShanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 200032China Bio-X-Renji Hospital Research CenterRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200240China Zhangjiang Institute for Advanced StudyShanghai Jiao Tong UniversityShanghai 200240China.
出 版 物：《Fundamental Research》 (自然科学基础研究（英文版）)
年 卷 期：2023年第3卷第4期
页 面：505-519页
核心收录：
学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学]
基 金：This work was supported by the National Natural Science Foundation of China(NSFC)(82188101,32171236,and 31872716 to C.L.,32170683 to D.L.) the Science and Technology Commission of Shanghai Municipality(STCSM)(20XD1425000 and 2019SHZDZX02 to C.L.) the Shanghai Pilot Program for Basic Research–Chinese Academy of Science,Shanghai Branch(CYJ-SHFY-2022-005)。
主 题：Amyloid aggregation Neurodegenerative diseases Clinical diagnosis Alzheimer’s disease Positron emission tomography(PET)tracer Tau Biomarker Post-translational modification
摘 要：Abnormal aggregation and accumulation of pathological amyloid proteins such as amyloid-β,Tau,and𝛼α-synuclein play key pathological roles and serve as histological hallmarks in different neurodegenerative diseases(NDs)such as Alzheimer’s disease(AD)and Parkinson’s disease(PD).In addition,various post-translational modifications(PTMs)have been identified on pathological amyloid proteins and are subjected to change during disease progression.Given the central role of amyloid proteins in NDs,tremendous efforts have been made to develop amyloid-targeting strategies for clinical diagnosis and molecular classification of NDs.In this review,we summarize two major strategies for targeting amyloid aggregates,with a focus on the trials in AD diagnosis.The first strategy is a positron emission tomography(PET)scan of protein aggregation in the brain.We mainly focus on introducing the development of small-molecule PET tracers for specifically recognizing pathological amyloid fibrils.The second strategy is the detection of PTM biomarkers on amyloid proteins in cerebrospinal fluid and plasma.We discuss the pathological roles of different PTMs in diseases and how we can use the PTM profile of amyloid proteins for clinical diagnosis.Finally,we point out the potential technical challenges of these two strategies,and outline other potential strategies,as well as a combination of multiple strategies,for molecular diagnosis of NDs.
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