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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F21%3A00550907" target="_blank" >RIV/68378041:_____/21:00550907 - isvavai.cz</a>

Result on the web

<a href="https://www.nature.com/articles/s41380-019-0608-9" target="_blank" >https://www.nature.com/articles/s41380-019-0608-9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41380-019-0608-9" target="_blank" >10.1038/s41380-019-0608-9</a>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30103 - Neurosciences (including psychophysiology)

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Molecular Psychiatry

ISSN

1359-4184

e-ISSN

1476-5578

Volume of the periodical

26

Issue of the periodical within the volume

2

Country of publishing house

GB - UNITED KINGDOM

Number of pages

12

Pages from-to

556-567

UT code for WoS article

000613804500017

EID of the result in the Scopus database

2-s2.0-85075429616