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.
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)。