A panel of epitope-specific antibodies detects protein domains distributed throughout human ?-synuclein in lewy bodies of Parkinson's disease

TLDR

α‑Synuclein is a major component of Lewy bodies in Parkinson’s disease, dementia with Lewy bodies, and common variants of Alzheimer’s disease. The authors generated and characterized a panel of anti‑synuclein antibodies to facilitate studies of α‑synuclein biology and to elucidate its pathological role in neurodegenerative diseases. The panel was generated and characterized by producing antibodies that recognize defined epitopes across the entire length of human α‑synuclein. The panel recognizes epitopes across human α‑synuclein, cross‑reacts with zebra finch and rodent synucleins, labels numerous Lewy bodies in the Parkinson’s disease substantia nigra, and can be used to probe normal biology and pathological roles of α‑synuclein in Parkinson’s disease and related synucleinopathies. © 2000 Wiley‑Liss, Inc., J.

Abstract

To facilitate studies of the normal biology of α-synuclein, a member of a family of neuronal proteins of unknown function, and to elucidate the role of α-synuclein pathologies in neurodegenerative diseases, we generated and characterized a panel of anti-synuclein antibodies. Here we demonstrate that these antibodies recognize defined epitopes spanning the entire length of human α-synuclein, and that some of these antibodies also cross-react with zebra finch and rodent synucleins. Since α-synuclein has been reported to be a major component of Lewy bodies (LBs) in Parkinson's disease (PD), dementia with LBs and common variants of Alzheimer's disease, we performed immunohistochemical studies showing that these antibodies label numerous LBs in the PD substantia nigra, thereby localizing protein domains throughout human α-synuclein in LBs. Taken together, our data indicate that this panel of antibodies can be exploited to probe the normal biology of α-synuclein as well as the role of pathological forms of this protein in PD and related neurodegenerative synucleinopathies. J. Neurosci. Res. 59:528–533, 2000 © 2000 Wiley-Liss, Inc.