Systemic alpha-synuclein injection triggers selective neuronal pathology as seen in patients with Parkinson's disease

0550907 - ÚEM 2022 RIV GB eng J - Journal Article
Kuan, K.L. - Stott, K. - He, X. - Wood, T.C. - Yang, S. - Kwok, Jessica - Hall, K. - Zhao, Y. - Tietz, O. - Aigbirhio, F.I. - Vernon, A.C. - Barker, R.A.
Systemic alpha-synuclein injection triggers selective neuronal pathology as seen in patients with Parkinson's disease.
Molecular Psychiatry. Roč. 26, č. 2 (2021), s. 556-567. ISSN 1359-4184. E-ISSN 1476-5578
Institutional support: RVO:68378041
Keywords : parkinson’s disease * transvascular delivery * alfa synuclein * neurodegeneration
OECD category: Neurosciences (including psychophysiology
Impact factor: 13.437, year: 2021
Method of publishing: Open access
https://www.nature.com/articles/s41380-019-0608-9

Parkinson's disease (PD) is an alpha-synucleinopathy characterized by the progressive loss of specific neuronal populations. Here, we develop a novel approach to transvascularly deliver proteins of complex quaternary structures, including alpha-synuclein preformed fibrils (pff). We show that a single systemic administration of alpha-synuclein pff triggers pathological transformation of endogenous alpha-synuclein in non-transgenic rats, which leads to neurodegeneration in discrete brain regions. Specifically, pff-exposed animals displayed a progressive deterioration in gastrointestinal and olfactory functions, which corresponded with the presence of cellular pathology in the central and enteric nervous systems. The alpha-synuclein pathology generated was both time dependent and region specific. Interestingly, the most significant neuropathological changes were observed in those brain regions affected in the early stages of PD. Our data therefore demonstrate for the first time that a single, transvascular administration of alpha-synuclein pff can lead to selective regional neuropathology resembling the premotor stage of idiopathic PD. Furthermore, this novel delivery approach could also be used to deliver a range of other pathogenic, as well as therapeutic, protein cargos transvascularly to the brain.
Permanent Link: http://hdl.handle.net/11104/0327949