ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2021
Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 14 citations in OpenAlex.
- Atmospheric Aerosol Neurotoxicity and Parkinson's Disease: Mechanisms and Perspectives.Journal of biochemical and molecular toxicology · 2026Review
- 25International journal of molecular sciences · 2026Article
- In silico prediction, molecular docking, and dynamics analysis of steroidal alkaloids from the genus Fritillaria: implications for designing novel antiparkinsonian therapeutic strategies.Scientific reports · 2026Article
- Novel Insights on Benzo[Antioxidants (Basel, Switzerland) · 2026Article
- RNA G‑Quadruplex Reprogramming with Guanine-Rich Antisense Oligonucleotides Inhibits Monoamine Oxidase B's Translation.ACS bio & med chem Au · 2025Article
- Exploring α-Syn's Functions Through Ablation Models: Physiological and Pathological Implications.Cellular and molecular neurobiology · 2025Review
- Monoamine Oxidase Inhibitors in Toxic Models of Parkinsonism.International journal of molecular sciences · 2025Review
- A crazy trio in Parkinson's disease: metabolism alteration, α-synuclein aggregation, and oxidative stress.Molecular and cellular biochemistry · 2025Review
- Decoding crosstalk between neurotransmitters and α-synuclein in Parkinson's disease: pathogenesis and therapeutic implications.Therapeutic advances in neurological disorders · 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
- Toxic interactions between dopamine, α-synuclein, monoamine oxidase, and genes in mitochondria of Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Recombinant adeno-associated virus 8-mediated inhibition of microRNA let-7a ameliorates sclerosing cholangitis in a clinically relevant mouse model.World journal of gastroenterology · 2024Article
- Genetic modifiers of synucleinopathies-lessons from experimental models.Oxford open neuroscience · 2023Review
- Neuroprotective Function of Rasagiline and Selegiline, Inhibitors of Type B Monoamine Oxidase, and Role of Monoamine Oxidases in Synucleinopathies.International journal of molecular sciences · 2022Review
- Chalcones as Potential Ligands for the Treatment of Parkinson's Disease.Pharmaceuticals (Basel, Switzerland) · 2022Review
- A critical appraisal of MAO-B inhibitors in the treatment of Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2022Review
- Altered protein secretion in Batten disease.Disease models & mechanisms · 2021Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cell-to-cell transmission of α-synuclein (α-syn) pathology is considered to underlie the spread of neurodegeneration in Parkinson's disease (PD). Previous studies have demonstrated that α-syn is secreted under physiological conditions in neuronal cell lines and primary neurons. However, the molecular mechanisms that regulate extracellular α-syn secretion remain unclear. In this study, we found that inhibition of monoamine oxidase-B (MAO-B) enzymatic activity facilitated α-syn secretion in human neuroblastoma SH-SY5Y cells. Both inhibition of MAO-B by selegiline or rasagiline and siRNA-mediated knock-down of MAO-B facilitated α-syn secretion. However, TVP-1022, the S-isomer of rasagiline that is 1000 times less active, failed to facilitate α-syn secretion. Additionally, the MAO-B inhibition-induced increase in α-syn secretion was unaffected by brefeldin A, which inhibits endoplasmic reticulum (ER)/Golgi transport, but was blocked by probenecid and glyburide, which inhibit ATP-binding cassette (ABC) transporter function. MAO-B inhibition preferentially facilitated the secretion of detergent-insoluble α-syn protein and decreased its intracellular accumulation under chloroquine-induced lysosomal dysfunction. Moreover, in a rat model (male Sprague Dawley rats) generated by injecting recombinant adeno-associated virus (rAAV)-A53T α-syn, subcutaneous administration of selegiline delayed the striatal formation of Ser129-phosphorylated α-syn aggregates, and mitigated loss of nigrostriatal dopaminergic neurons. Selegiline also delayed α-syn aggregation and dopaminergic neuronal loss in a cell-to-cell transmission rat model (male Sprague Dawley rats) generated by injecting rAAV-wild-type α-syn and externally inoculating α-syn fibrils into the striatum. These findings suggest that MAO-B inhibition modulates the intracellular clearance of detergent-insoluble α-syn via the ABC transporter-mediated non-classical secretion pathway, and temporarily suppresses the formation and transmission of α-syn aggregates.
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