Glycated α-Synuclein Renders Glial Cell Activation and Induces Degeneration of Dopaminergic Neurons: A Potential Implication for the Development of Parkinson's Disease
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F25%3A00082295" target="_blank" >RIV/00159816:_____/25:00082295 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14110/25:00140705
Result on the web
<a href="https://pubs.acs.org/doi/10.1021/acschembio.4c00777" target="_blank" >https://pubs.acs.org/doi/10.1021/acschembio.4c00777</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acschembio.4c00777" target="_blank" >10.1021/acschembio.4c00777</a>
Alternative languages
Result language
angličtina
Original language name
Glycated α-Synuclein Renders Glial Cell Activation and Induces Degeneration of Dopaminergic Neurons: A Potential Implication for the Development of Parkinson's Disease
Original language description
Accumulation of misfolded alpha-synuclein (alpha-Syn) leads to the formation of Lewy bodies and is a major hallmark of Parkinson's disease (PD). The accumulation of alpha-Syn involves several post-translational modifications. Recently, though, glycation of alpha-Syn (advanced glycation end products) and activation of the receptor for advanced glycation end products (RAGE) have been linked to neuroinflammation, which leads to oxidative stress and accumulation of alpha-Syn. The present study aims to detect the effect of glycated alpha-Syn (gly-alpha-Syn)-induced synucleinopathy and loss of dopaminergic (DAergic) neurons in the development of PD. We isolated, purified, and prepared glycated recombinant human alpha-Syn using d-ribose. Gly-alpha-Syn was characterized by SDS-PAGE, intact mass analysis, and bottom-up peptide sequence through LC-HRMS/MS. The aggregation propensity of gly-alpha-Syn has been verified by morphological and shape analysis through Bio-AFM. The gly-alpha-Syn (2 mu g/mu L) was injected stereotaxically in the substantia nigra (SN) of ICR mice (3-4 months) and compared with the normal alpha-Syn, d ribose, and Tris-HCl/artificial CSF groups. 56 days postsurgery (DPS), an immunohistochemical examination was conducted to investigate gly-alpha-Syn-induced alpha-Syn accumulation, neuroinflammation, and neurodegeneration. The glycation of alpha-Syn led to the expression of transglutaminase 2 (TGM2), an enzyme that cross-linked with AGEs and may have caused the accumulation of alpha-Syn. Significant RAGE activation was also observed in gly-alpha-Syn, which might have induced glial cell activation, resulting in oxidative stress and, ultimately, apoptosis of dopaminergic neurons. It is important to note that TGM2, phosphorylated alpha-Syn, RAGE expression, and glial cell activation were only found in the gly-alpha-Syn group and not in the other groups. This suggests that gly-alpha-Syn plays a major role in synucleinopathy, neuroinflammation, and neurodegeneration. Overall, the present study demonstrated glycation of alpha-Syn as one of the important age-associated post-translational modifications that are involved in the degeneration of dopaminergic neurons, at least in a subset of the diabetic patients susceptible to developing PD.
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
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/LX22NPO5107" target="_blank" >LX22NPO5107: National institute for Neurological Research</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
ACS Chemical Biology
ISSN
1554-8929
e-ISSN
1554-8937
Volume of the periodical
20
Issue of the periodical within the volume
3
Country of publishing house
US - UNITED STATES
Number of pages
14
Pages from-to
632-645
UT code for WoS article
001431190400001
EID of the result in the Scopus database
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