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Prudente de Mello, N. ; Berger, M. ; Lagerborg, K.A.* ; Yan, Y. ; Wettmarshausen, J. ; Keipert, S.* ; Weidner, L. ; Tokarz, J. ; Möller, G. ; Ciciliot, S.* ; Walia, S.R. ; Cheng, Y. ; Chudenkova, M. ; Artati, A. ; Weisenhorn, D.M. ; Wurst, W. ; Adamski, J. ; Nilsson, R.H.* ; Cossu, G.* ; Boon, A.J.W.* ; Kievit, A.J.A.* ; Mandemakers, W.* ; Bonifati, V.* ; Jain, M.* ; Jastroch, M.* ; Schmitt-Kopplin, P. ; Perocchi, F. ; Dyar, K.A.

Pervasive glycative stress links metabolic imbalance and muscle atrophy in early-onset Parkinson's disease.

Mol. Metab. 97:102163 (2025)

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Parkinson's disease (PD) is recognized as a systemic condition, with clinical features potentially modifiable by dietary intervention. Diets high in saturated fats and refined sugars significantly increase PD risk and exacerbate motor and non-motor symptoms, yet precise metabolic mechanisms are unclear. To investigate the interplay between diet and PD, we used a model of early-onset PD under chronic glycative stress induced by prolonged high-fat high-sucrose (HFHS) diet. We found this obesogenic diet drives loss of fat and muscle mass in early-onset PD mice, with a selective vulnerability of glycolytic myofibers. We show that PD mice and early-onset familial PD patients are under pervasive glycative stress with pathological accumulation of advanced glycation end products (AGEs), including two previously unknown glycerinyl-AGE markers.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Advanced Glycation Endproducts (ages) ; Biomarkers ; Glycative Stress ; Glycobiology ; Muscle Atrophy ; Parkinson's Disease; Dj-1; Age

ISSN (print) / ISBN 2212-8778

e-ISSN 2212-8778

Journal Molecular Metabolism

Quellenangaben Volume: 97, Article Number: 102163

Publisher Elsevier

Publishing Place Amsterdam

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes and Cancer (IDC)
Institute of Diabetes and Obesity (IDO)
Research Unit BioGeoChemistry and Analytics (BGC)
CF Metabolomics & Proteomics (CF-MPC)
Institute of Developmental Genetics (IDG)
Institute of Experimental Genetics (IEG)

Grants Stichting Parkinson Fonds
Munich Graduate School of Systemic Neurosciences
Munich Center for Systems Neurology
Deutsches Zentrum fur Diabetesforschung
ExNet-0041-Phase2-3 through the Initiative and Network Fund of the Helmholtz Association (SyNergy-HMGU)