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Systemic alpha-synuclein injection triggers selective neuronal pathology as seen in patients with Parkinson's disease
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SYSNO ASEP 0550907 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Systemic alpha-synuclein injection triggers selective neuronal pathology as seen in patients with Parkinson's disease Tvůrce(i) Kuan, K.L. (GB)
Stott, K. (GB)
He, X. (GB)
Wood, T.C. (GB)
Yang, S. (GB)
Kwok, Jessica (UEM-P) ORCID, RID
Hall, K. (GB)
Zhao, Y. (GB)
Tietz, O. (GB)
Aigbirhio, F.I. (GB)
Vernon, A.C. (GB)
Barker, R.A. (GB)Zdroj.dok. Molecular Psychiatry. - : Springer - ISSN 1359-4184
Roč. 26, č. 2 (2021), s. 556-567Poč.str. 12 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova parkinson’s disease ; transvascular delivery ; alfa synuclein ; neurodegeneration Vědní obor RIV FH - Neurologie, neurochirurgie, neurovědy Obor OECD Neurosciences (including psychophysiology Způsob publikování Open access Institucionální podpora UEM-P - RVO:68378041 UT WOS 000613804500017 EID SCOPUS 85075429616 DOI 10.1038/s41380-019-0608-9 Anotace 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. Pracoviště Ústav experimentální medicíny Kontakt Lenka Koželská, lenka.kozelska@iem.cas.cz, Tel.: 241 062 218, 296 442 218 Rok sběru 2022 Elektronická adresa https://www.nature.com/articles/s41380-019-0608-9
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