A scFv antibody targeting common oligomeric epitope has potential for treating several amyloidoses.
Overproduction or poor clearance of amyloids lead to amyloid aggregation and even amyloidosis development. Different amyloids may interact synergistically to promote their aggregation and accelerate pathology in amyloidoses. Amyloid oligomers assembled from different amyloids share common structures and epitopes, and are considered the most toxic species in the pathologic processes of amyloidoses, which suggests that an agent targeting the common epitope of toxic oligomers could provide benefit to several amyloidoses. In this study, we firstly showed that an oligomer-specific single-chain variable fragment antibody, W20 simultaneously improved motor and cognitive function in Parkinson's disease and Huntington's disease mouse models, and attenuated a number of neuropathological features by reducing α-synuclein and mutant huntingtin protein aggregate load and preventing synaptic degeneration. Neuroinflammation and oxidative stress in vivo were also markedly inhibited. The proposed strategy targeting the common epitopes of amyloid oligomers presents promising potential for treating Parkinson's disease, Huntington's disease, Alzheimer's disease, and other amyloidoses.
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China.|School of Pharmacy, China Pharmaceutical University, Nanjing, China.
Jun
J
Zha
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China.|School of Bioengineering, Qilu University of Technology, Jinan, China.
Xiang-Meng
XM
Liu
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China.
Jie
J
Zhu
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China.|School of Life Science, Ningxia University, Yinchuan, China.
Shu-Ying
SY
Liu
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China.
Shuai
S
Lu
School of Life Science, Ningxia University, Yinchuan, China.
Peng-Xin
PX
Xu
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China.
Xiao-Lin
XL
Yu
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China.
Rui-Tian
RT
Liu
D000682:Amyloid / Q000276:immunology*; D000686:Amyloidosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D003071:Cognition / Q000187:drug effects*; D000939:Epitopes / Q000276:immunology*; D006816:Huntington Disease / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000187:drug effects* / Q000276:immunology; D010302:Parkinson Disease, Secondary / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D057127:Single-Chain Antibodies / Q000276:immunology / Q000494:pharmacology*
D000682:Amyloid; D000939:Epitopes; D057127:Single-Chain Antibodies