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000279047 1001_ $$ade Mello, Natalia Prudente$$b0
000279047 245__ $$aPervasive glycative stress links metabolic imbalance and muscle atrophy in early-onset Parkinson's disease.
000279047 260__ $$aOxford [u.a.]$$bElsevier$$c2025
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000279047 520__ $$aParkinson's disease (PD) is recognized as a systemic condition, with clinical features potentially modifiable by dietary intervention. Diets high in saturated fats and refined sugars significantly increase PD risk and exacerbate motor and non-motor symptoms, yet precise metabolic mechanisms are unclear. Our objective here was to investigate the interplay between diet and PD-associated phenotypes from a metabolic perspective.We explored PARK7 KO mice under chronic glycative stress induced by prolonged high-fat high-sucrose (HFHS) diet. We investigated metabolic consequences by combining classical metabolic phenotyping (body composition, glucose tolerance, indirect calorimetry, functional assays of isolated mitochondria) with metabolomics profiling of biospecimens from mice and PD patients.We found this obesogenic diet drives loss of fat and muscle mass in early-onset PD mice, with a selective vulnerability of glycolytic myofibers. We show that PD mice and early-onset familial PD patients are under pervasive glycative stress with pathological accumulation of advanced glycation end products (AGEs), including N-α-glycerinylarginine (α-GR) and N-α-glycerinyllysine (α-GK), two previously unknown glycerinyl-AGE markers.Our results offer the first proof for a direct link between diet, accumulation of AGEs and genetics of PD. We also expand the repertoire of clinically-relevant glycative stress biomarkers to potentially define at-risk patients before neurological or metabolic symptoms arise, and/or to monitor disease onset, progression, and effects of interventions.
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000279047 650_7 $$2Other$$aAdvanced glycation endproducts (AGEs)
000279047 650_7 $$2Other$$aBiomarkers
000279047 650_7 $$2Other$$aGlycative stress
000279047 650_7 $$2Other$$aGlycobiology
000279047 650_7 $$2Other$$aMuscle atrophy
000279047 650_7 $$2Other$$aParkinson's disease
000279047 650_7 $$2NLM Chemicals$$aGlycation End Products, Advanced
000279047 650_2 $$2MeSH$$aAnimals
000279047 650_2 $$2MeSH$$aMice
000279047 650_2 $$2MeSH$$aParkinson Disease: metabolism
000279047 650_2 $$2MeSH$$aHumans
000279047 650_2 $$2MeSH$$aMale
000279047 650_2 $$2MeSH$$aDiet, High-Fat: adverse effects
000279047 650_2 $$2MeSH$$aMuscular Atrophy: metabolism
000279047 650_2 $$2MeSH$$aMice, Knockout
000279047 650_2 $$2MeSH$$aGlycation End Products, Advanced: metabolism
000279047 650_2 $$2MeSH$$aFemale
000279047 650_2 $$2MeSH$$aMice, Inbred C57BL
000279047 650_2 $$2MeSH$$aMetabolomics: methods
000279047 650_2 $$2MeSH$$aMuscle, Skeletal: metabolism
000279047 650_2 $$2MeSH$$aDisease Models, Animal
000279047 7001_ $$aBerger, Michelle Tamara$$b1
000279047 7001_ $$aLagerborg, Kim A$$b2
000279047 7001_ $$aYan, Yingfei$$b3
000279047 7001_ $$aWettmarshausen, Jennifer$$b4
000279047 7001_ $$aKeipert, Susanne$$b5
000279047 7001_ $$aWeidner, Leopold$$b6
000279047 7001_ $$aTokarz, Janina$$b7
000279047 7001_ $$aMöller, Gabriele$$b8
000279047 7001_ $$aCiciliot, Stefano$$b9
000279047 7001_ $$aWalia, Safal$$b10
000279047 7001_ $$aCheng, Yiming$$b11
000279047 7001_ $$aChudenkova, Margarita$$b12
000279047 7001_ $$aArtati, Anna$$b13
000279047 7001_ $$aWeisenhorn, Daniela Vogt$$b14
000279047 7001_ $$0P:(DE-2719)2000028$$aWurst, Wolfgang$$b15$$udzne
000279047 7001_ $$aAdamski, Jerzy$$b16
000279047 7001_ $$aNilsson, Roland$$b17
000279047 7001_ $$aCossu, Giovanni$$b18
000279047 7001_ $$aBoon, Agnita$$b19
000279047 7001_ $$aKievit, Anneke$$b20
000279047 7001_ $$aMandemakers, Wim$$b21
000279047 7001_ $$aBonifati, Vincenzo$$b22
000279047 7001_ $$aJain, Mohit$$b23
000279047 7001_ $$aJastroch, Martin$$b24
000279047 7001_ $$aSchmitt-Kopplin, Philippe$$b25
000279047 7001_ $$aPerocchi, Fabiana$$b26
000279047 7001_ $$aDyar, Kenneth Allen$$b27
000279047 773__ $$0PERI:(DE-600)2708735-9$$a10.1016/j.molmet.2025.102163$$gVol. 97, p. 102163 -$$p102163$$tMolecular metabolism$$v97$$x2212-8778$$y2025
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