ArticleThe EMBO journal2018
α-Synuclein stimulation of monoamine oxidase-B and legumain protease mediates the pathology of Parkinson's disease.
Article in The EMBO journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
59 citing papers in PubMed, 96 citations in OpenAlex.
- Neuroinflammation and noradrenergic modulation with β2-adrenoceptors: Emerging therapeutic targets for Parkinson's diseases.Neural regeneration research · 2026Article
- Rational Design of Multifunctional Tacrine Derivatives as Candidates for the Treatment of Alzheimer and Parkinson Diseases.ChemMedChem · 2026Article
- Low-Dose Ionizing Radiation and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Review of Recent Evidence and Future Research Directions Toward the Elucidation of a Metabolic, Immunologic, and Signaling Cascade.International journal of molecular sciences · 2026Review
- Mechanistic insights into anti-parkinson effect of baicalein: from neuroinflammation and cell death to neurogenesis and synaptic plasticity.Molecular biology reports · 2026Review
- Internalized SNCA/α-synuclein fibrils become truncated and resist degradation in neurons while glial cells rapidly degrade SNCA fibrils.Autophagy · 2026Article
- Synaptic Changes in Mice Lacking Alpha- and Gamma-Synucleins.Biomedicines · 2025Article
- Disruption of axonal transport in Parkinson's disease: the role of pathological α-Syn and AMPK/p38 MAPK signaling.NPJ Parkinson's disease · 2025Article
- A Focus on the Link Between Metal Dyshomeostasis, Norepinephrine, and Protein Aggregation.Antioxidants (Basel, Switzerland) · 2025Review
- Monoamine Oxidase Inhibitors in Toxic Models of Parkinsonism.International journal of molecular sciences · 2025Review
- Decoding crosstalk between neurotransmitters and α-synuclein in Parkinson's disease: pathogenesis and therapeutic implications.Therapeutic advances in neurological disorders · 2025Review
- Sox6 and ALDH1A1 Truncation by Asparagine Endopeptidase Defines Selective Neuronal Vulnerability in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Roles of C/EBPβ/AEP in Neurodegenerative Diseases.Current topics in medicinal chemistry · 2025Review
- Exploring the 1-(4-Nitrophenyl)-3-arylprop-2-en-1-one Scaffold for the Selective Inhibition of Monoamine Oxidase B.ACS medicinal chemistry letters · 2024Article
- Complicated Role of Post-translational Modification and Protease-Cleaved Fragments of Tau in Alzheimer's Disease and Other Tauopathies.Molecular neurobiology · 2024Review
- Toxic interactions between dopamine, α-synuclein, monoamine oxidase, and genes in mitochondria of Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Role of Epigenetic Modulation in Neurodegenerative Diseases: Implications of Phytochemical Interventions.Antioxidants (Basel, Switzerland) · 2024Review
- Article
- Cholestanol accelerates α-synuclein aggregation and spreading by activating asparagine endopeptidase.JCI insight · 2023Article
- Inhibition of abnormal C/EBPβ/α-Syn signaling pathway through activation of Nrf2 ameliorates Parkinson's disease-like pathology.Aging cell · 2023Article
- Loss of DJ-1 function contributes to Parkinson's disease pathogenesis in mice via RACK1-mediated PKC activation and MAO-B upregulation.Acta pharmacologica Sinica · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Dopaminergic neurodegeneration in Parkinson's disease (PD) is associated with abnormal dopamine metabolism by MAO-B (monoamine oxidase-B) and intracellular α-Synuclein (α-Syn) aggregates, called the Lewy body. However, the molecular relationship between α-Syn and MAO-B remains unclear. Here, we show that α-Syn directly binds to MAO-B and stimulates its enzymatic activity, which triggers AEP (asparagine endopeptidase; legumain) activation and subsequent α-Syn cleavage at N103, leading to dopaminergic neurodegeneration. Interestingly, the dopamine metabolite, DOPAL, strongly activates AEP, and the N103 fragment of α-Syn binds and activates MAO-B. Accordingly, overexpression of AEP in SNCA transgenic mice elicits α-Syn N103 cleavage and accelerates PD pathogenesis, and inhibition of MAO-B by Rasagiline diminishes α-Syn-mediated PD pathology and motor dysfunction. Moreover, virally mediated expression of α-Syn N103 induces PD pathogenesis in wild-type, but not MAO-B-null mice. Our findings thus support that AEP-mediated cleavage of α-Syn at N103 is required for the association and activation of MAO-B, mediating PD pathogenesis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.