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RAGE Against the Glycation Machine in Synucleinopathies: Time to Explore New Questions

Lookup NU author(s): Professor Tiago OuteiroORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


© 2023 - The authors. Published by IOS Press.Oligomerization and aggregation of misfolded forms of α-synuclein are believed to be key molecular mechanisms in Parkinson's disease (PD) and other synucleinopathies, so extensive research has attempted to understand these processes. Among diverse post-translational modifications that impact α-synuclein aggregation, glycation may take place at several lysine sites and modify α-synuclein oligomerization, toxicity, and clearance. The receptor for advanced glycation end products (RAGE) is considered a key regulator of chronic neuroinflammation through microglial activation in response to advanced glycation end products, such as carboxy-ethyl-lysine, or carboxy-methyl-lysine. The presence of RAGE in the midbrain of PD patients has been reported in the last decades and this receptor was proposed to have a role in sustaining PD neuroinflammation. However, different PD animal models demonstrated that RAGE is preferentially expressed in neurons and astrocytes, while recent evidence demonstrated that fibrillar, non-glycated α-synuclein binds to RAGE. Here, we summarize the available data on α-synuclein glycation and RAGE in the context of PD, and discuss about the questions yet to be answered that may increase our understanding of the molecular bases of PD and synucleinopathies.

Publication metadata

Author(s): Gelain DP, Bittencourt RR, Bastos Mendes LF, Moreira JCF, Outeiro TF

Publication type: Article

Publication status: Published

Journal: Journal of Parkinson's Disease

Year: 2023

Volume: 13

Issue: 5

Pages: 717-728

Online publication date: 25/07/2023

Acceptance date: 13/05/2023

Date deposited: 12/09/2023

ISSN (print): 1877-7171

ISSN (electronic): 1877-718X

Publisher: IOS Press BV


DOI: 10.3233/JPD-230070

PubMed id: 37270812


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Funder referenceFunder name
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
EXC 2067/1-390729940
SFB1286 (B8)