Unveiling new secrets in Parkinson’s disease: The glycatome

• Published in: Behavioural brain research Vol. 442; p. 114309
• Main Authors: Chegão, Ana, Vicente Miranda, Hugo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 28.03.2023
• Subjects: Alpha-synuclein; alpha-Synuclein - metabolism; Diabetes Mellitus, Type 2 - complications; Glycation; Glycatome; Humans; Maillard Reaction; Parkinson Disease - metabolism; Parkinson’s disease; Type-2 diabetes; Type-2 diabetes; T2DM; PD; aSyn; Glycatome; Glycation; Alpha-synuclein; Parkinson’s disease; AGE
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2023.114309

We are witnessing a considerable increase in the incidence of Parkinson’s disease (PD), which may be due to the general ageing of the population. While there is a plethora of therapeutic strategies for this disease, they still fail to arrest disease progression as they do not target and prevent the neurodegenerative process. The identification of disease-causing mutations allowed researchers to better dissect the underlying causes of this disease, highlighting, for example, the pathogenic role of alpha-synuclein. However, most PD cases are sporadic, which is making it hard to unveil the major causative mechanisms of this disease. In the recent years, epidemiological evidence suggest that type-2 diabetes mellitus (T2DM) individuals have higher risk and worst outcomes of PD, allowing to raise the hypothesis that some dysregulated processes in T2DM may contribute or even trigger the neurodegenerative process in PD. One major consequence of T2DM is the unprogrammed reaction between sugars, increased in T2DM, and proteins, a reaction named glycation. Pre-clinical reports show that alpha-synuclein is a target of glycation, and glycation potentiates its pathogenicity which contributes for the neurodegenerative process. Moreover, it triggers, anticipates, or aggravates several PD-like motor and non-motor complications. A given profile of proteins are differently glycated in diseased conditions, altering the brain proteome and leading to brain dysfunction and neurodegeneration. Herein we coin the term Glycatome as the profile of glycated proteins. In this review we report on the mechanisms underlying the association between T2DM and PD, with particular focus on the impact of protein glycation. •Glycation-associated alterations may underly the association between type-2 diabetes and Parkinson’s disease.•Glycatome is defined as the profile of glycated proteins.•Glycatome alterations may trigger the dysfunction of PD-associated alterations.•Glycation induces alpha-synuclein pathogenesis and dysregulates several components of glutamatergic signalling.