ArticleNPJ Parkinson's disease2022
Harmol promotes α-synuclein degradation and improves motor impairment in Parkinson's models via regulating autophagy-lysosome pathway.
Article in NPJ Parkinson's disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Are Therapies That Target α-Synuclein Effective at Halting Parkinson's Disease Progression? A Systematic Review.International journal of molecular sciences · 2023Pooled it
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Low-intensity transcranial ultrasound stimulation suppresses abnormal neural oscillations in the motor cortex by stimulating STN in α-synucleinActa neuropathologica communications · 2026Article
- Irisin-integrin αV/β5 coupling of α-synuclein phagocytosis and clearance.Journal of neuroinflammation · 2026Article
- Review
- Leveraging mitochondrial stress to improve healthy aging.Sports medicine and health science · 2026Review
- R406 and its structural analogs reduce SNCA/α-synuclein levels via autophagic degradation.Autophagy · 2025Article
- Recent Advances in Autophagy and Immunotherapy for the Clearance of Aggregated α-Synuclein in Parkinson's Disease.Aging and disease · 2025Review
- Synaptic sabotage: How Tau and α-Synuclein undermine synaptic health.The Journal of cell biology · 2025Review
- Ginsenoside Rg1 ameliorates stress-exacerbated Parkinson's disease in mice by eliminating RTP801 and α-synuclein autophagic degradation obstacle.Acta pharmacologica Sinica · 2025Article
- Immunomodulatory therapy for sepsis: from pathophysiological mechanisms to precision treatment.Frontiers in cellular and infection microbiology · 2025Review
- Natural autophagy modulators in non-communicable diseases: from autophagy mechanisms to therapeutic potential.Acta pharmacologica Sinica · 2025Review
- Harmol used for the treatment of herpes simplex virus induced keratitis.Virology journal · 2024Article
- Olfactory dysfunction and its related molecular mechanisms in Parkinson's disease.Neural regeneration research · 2024Review
- The Role of Immune Dysfunction in Parkinson's Disease Development.International journal of molecular sciences · 2023Review
- Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The abnormal accumulation of α-synuclein (α-syn) is a crucial factor for the onset and pathogenesis of Parkinson's disease (PD), and the autophagy-lysosome pathway (ALP) contributes to α-syn turnover. AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR) regulate autophagy by initiating the macroautophagy cascade and promoting lysosomal biogenesis via increased transcription factor EB (TFEB) activity. Hence, activation of AMPK-mTOR-TFEB axis-mediated autophagy might promote α-syn clearance in PD. Harmol is a β-carboline alkaloid that has been extensively studied in a variety of diseases but rarely in PD models. In this study, we aimed to evaluate the effect and underlying mechanism of harmol in PD models in vitro and in vivo. We show that harmol reduces α-syn via ALP in a dose- and time-dependent manner in cell model that overexpressed human A53T mutant α-syn. We also demonstrate that harmol promotes the translocation of TFEB into the nucleus and accompanies the restoration of autophagic flux and lysosomal biogenesis. Importantly, harmol improves motor impairment and down-regulates α-syn levels in the substantia nigra and prefrontal cortex in the α-syn transgenic mice model. Further studies revealed that harmol might activate ALP through AMPK-mTOR-TFEB to promote α-syn clearance. These in vitro and in vivo improvements demonstrate that harmol activates the AMPK-mTOR-TFEB mediated ALP pathway, resulting in reduced α-syn, and suggesting the potential benefit of harmol in the treatment of PD.
Identifiers
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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.