Toxicity of extracellular alpha-synuclein is independent of intracellular alpha-synuclein
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F22%3A00133949" target="_blank" >RIV/00216224:14740/22:00133949 - isvavai.cz</a>
Result on the web
<a href="https://www.nature.com/articles/s41598-022-25790-2" target="_blank" >https://www.nature.com/articles/s41598-022-25790-2</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41598-022-25790-2" target="_blank" >10.1038/s41598-022-25790-2</a>
Alternative languages
Result language
angličtina
Original language name
Toxicity of extracellular alpha-synuclein is independent of intracellular alpha-synuclein
Original language description
Parkinson ' s disease (PD) pathology progresses throughout the nervous system. Whereas motor symptoms are always present, there is a high variability in the prevalence of non-motor symptoms. It has been postulated that the progression of the pathology is based on a prion-like disease mechanism partly due to the seeding effect of endocytosed-alpha-synuclein (ASYN) on the endogenous ASYN. Here, we analyzed the role of endogenous ASYN in the progression of PD-like pathology in vivo and in vitro and compared the effect of endocytosed-ASYN as well as paraquat and rotenone on primary enteric, dopaminergic and cortical neurons from wild-type and ASYN-KO mice. Our results show that, in vivo, pathology progression did not occur in the absence of endogenous ASYN. Remarkably, the damage caused by endocytosed-ASYN, rotenone or paraquat was independent from endogenous ASYN and related to the alteration of the host ' s mitochondrial membrane potential. Dopaminergic neurons were very sensitive to these noxae compared to other neuronal subtypes. These results suggest that ASYN-mitochondrial interactions play a major role in initiating the pathological process in the host neuron and endogenous ASYN is essential for the transsynaptical transmission of the pathology. Our results also suggest that protecting mitochondrial function is a valid primary therapeutic target.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30103 - Neurosciences (including psychophysiology)
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature Scientific Reports
ISSN
2045-2322
e-ISSN
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Volume of the periodical
12
Issue of the periodical within the volume
1
Country of publishing house
DE - GERMANY
Number of pages
16
Pages from-to
1-16
UT code for WoS article
000971311200020
EID of the result in the Scopus database
2-s2.0-85144263595