Immunotherapy targeting α-synuclein, with relevance for future treatment of Parkinson's disease and other Lewy body disorders.
Immunotherapy targeting α-synuclein has evolved as a potential therapeutic strategy for neurodegenerative diseases, such as Parkinson's disease, and initial studies on cellular and animal models have shown promising results. α-synuclein vaccination of transgenic mice reduced the number of brain inclusions, whereas passive immunization studies demonstrated that antibodies against the C-terminus of α-synuclein can pass the blood-brain barrier and affect the pathology. In addition, preliminary evidence suggests that transgenic mice treated with an antibody directed against α-synuclein oligomers/protofibrils resulted in reduced levels of such species in the CNS. The underlying mechanisms of immunotherapy are not yet fully understood, but may include antibody-mediated clearance of pre-existing aggregates, prevention of protein propagation between cells and microglia-dependent protein clearance. Thus, immunotherapy targeting α-synuclein holds promise, but needs to be further developed as a future disease-modifying treatment in Parkinson's disease and other α-synucleinopathies.
Department of Public Health/Geriatrics, Rudbeck Laboratory, Uppsala University, 751 85 Uppsala, Sweden.
Veronica
V
Lindström
Elisabet
E
Ihse
Therese
T
Fagerqvist
Joakim
J
Bergström
Eva
E
Nordström
Christer
C
Möller
Lars
L
Lannfelt
Martin
M
Ingelsson
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000639:trends; D016631:Lewy Bodies / Q000378:metabolism*; D020961:Lewy Body Disease / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008822:Mice, Transgenic; D058990:Molecular Targeted Therapy; D010300:Parkinson Disease / Q000276:immunology / Q000628:therapy*; D056811:Unfolded Protein Response / Q000276:immunology; D051844:alpha-Synuclein / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; D051844:alpha-Synuclein