ArticleActa neuropathologica communications2022
Mitochondrial dysfunction is a key pathological driver of early stage Parkinson's.
Article in Acta neuropathologica communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 2 of them syntheses that pooled it.
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Who cites it
44 citing papers in PubMed, 2 syntheses or guidelines pooled it, 73 citations in OpenAlex.
- Omics research in Parkinson's disease: evolution, integrated analysis, pathogenic mechanisms, biomarkers, and therapeutic targets.Frontiers in molecular neuroscience · 2026Pooled it
- Meta-analysis of the serum/plasma proteome identifies significant associations between COVID-19 with Alzheimer's/Parkinson's diseases.Journal of neurovirology · 2024Pooled it
- Large-scale visualization of α-synuclein oligomers in Parkinson's disease brain tissue.Nature biomedical engineering · 2026Article
- Phosphorylated ubiquitin is a secondary messenger and an epigenetic mark mediating mitochondria to nucleus signaling.bioRxiv : the preprint server for biology · 2026Article
- Distinct metabolomic and proteomic signatures in Parkinson's disease patients with REM sleep behavior disorder.Signal transduction and targeted therapy · 2026Article
- Cerebrospinal fluid and plasma metabolites in Parkinson's disease: a Mendelian randomization study.Scientific reports · 2026Article
- VMAT2 dysfunction impairs vesicular dopamine uptake, driving its oxidation and α-synuclein pathology in DJ-1-linked Parkinson's neurons.Science advances · 2026Article
- Sodium Propionate Protects Dopaminergic Neurons Against Mitochondrial Toxin-Induced Oxidative Stress In Vitro.International journal of molecular sciences · 2026Article
- CCNE1 Exerts a Protective Effect on Parkinson's Disease by Regulating Ferroptosis-Related Proteins.Brain and behavior · 2025Article
- Integrative multiomics elucidate crotonylation-associated GCDH in Parkinson's disease pathogenesis via metabolome remodeling.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- The role of fatty acids in neurodegenerative diseases: mechanistic insights and therapeutic strategies.Journal of lipid research · 2025Review
- Multi-omic analysis reveals lipid dysregulation associated with mitochondrial dysfunction in parkinson's disease brain.Nature communications · 2025Article
- The Small Molecule DDOX Confers Neuroprotection and Alleviates Motor Deficits in a Preclinical Rat Model of Parkinson's Disease.Neurotoxicity research · 2025Article
- Peripheral Blood Mononuclear Cell Mitochondrial Bioenergetics Is Impaired in De Novo Parkinson's Disease.Molecular neurobiology · 2025Article
- Pre-treatment untargeted cerebrospinal fluid metabolomic profiling in tuberculous meningitis uncovers pathways associated with mortality.Med (New York, N.Y.) · 2025Article
- Parkinson's Disease Through the Lens of Metabolomics: A Targeted Systematic Review on Human Studies (2019-2024).Journal of clinical medicine · 2025Review
- Are Hippocampal Hypoperfusion and ATP Depletion Prime Movers in the Genesis of Alzheimer's Disease? A Review of Recent Pertinent Observations from Molecular Biology.International journal of molecular sciences · 2025Review
- Metabolic Dysregulation in Parkinson's Disease: Non-Oxidative Phosphorylation and Its Role in Brain Energy Metabolism.Aging and disease · 2025Review
- Neural Metabolic Networks: Key Elements of Healthy Brain Function.Journal of neurochemistry · 2025Review
- Application of IVDr NMR spectroscopy to stratify Parkinson's disease with absolute quantitation of blood serum metabolites and lipoproteins.Scientific reports · 2025Article
Corrections and comments
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Authors and funding
20 authors at 9 institutions in 5 countries.
Funding
Abstract
backgroundThe molecular drivers of early sporadic Parkinson's disease (PD) remain unclear, and the presence of widespread end stage pathology in late disease masks the distinction between primary or causal disease-specific events and late secondary consequences in stressed or dying cells. However, early and mid-stage Parkinson's brains (Braak stages 3 and 4) exhibit alpha-synuclein inclusions and neuronal loss along a regional gradient of severity, from unaffected-mild-moderate-severe. Here, we exploited this spatial pathological gradient to investigate the molecular drivers of sporadic PD.
methodsWe combined high precision tissue sampling with unbiased large-scale profiling of protein expression across 9 brain regions in Braak stage 3 and 4 PD brains, and controls, and verified these results using targeted proteomic and functional analyses.
resultsWe demonstrate that the spatio-temporal pathology gradient in early-mid PD brains is mirrored by a biochemical gradient of a changing proteome. Importantly, we identify two key events that occur early in the disease, prior to the occurrence of alpha-synuclein inclusions and neuronal loss: (i) a metabolic switch in the utilisation of energy substrates and energy production in the brain, and (ii) perturbation of the mitochondrial redox state. These changes may contribute to the regional vulnerability of developing alpha-synuclein pathology. Later in the disease, mitochondrial function is affected more severely, whilst mitochondrial metabolism, fatty acid oxidation, and mitochondrial respiration are affected across all brain regions.
conclusionsOur study provides an in-depth regional profile of the proteome at different stages of PD, and highlights that mitochondrial dysfunction is detectable prior to neuronal loss, and alpha-synuclein fibril deposition, suggesting that mitochondrial dysfunction is one of the key drivers of early disease.
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