ArticleMetabolic brain disease2022
AMPK-dependent autophagy activation and alpha-Synuclein clearance: a putative mechanism behind alpha-mangostin's neuroprotection in a rotenone-induced mouse model of Parkinson's disease.
Article in Metabolic brain disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Phosphatidylinositol-3-kinase/Protein Kinase B (PI3K/AKT) and Nucleotide-Binding Oligomerization Domain-like Receptor Family Pyrin Domain Containing 3 (NLRP3) Inflammasome Modulation Underlies the Neuroprotective Effects of Vildagliptin in a Rotenone-Induced Mouse Model of Parkinson's Disease.ACS pharmacology & translational science · 2026Article
- Sulforaphane-Mediated Multitarget Therapeutic Effects in Methylmercury-Induced ALS-Like Pathology: Comparative Analysis and Multifaceted Approach to Neuroprotection and Systemic Recovery.Molecular neurobiology · 2026Article
- Modulation of Bromo- and Extra-Terminal Domain (BET) Proteins Exerts Neuroprotective Effects in Cell Culture Models of Parkinson's Disease.Biomedicines · 2026Article
- Article
- OAB-14 Attenuated Glymphatic System Disorder, Neuroinflammation and Dyskinesia in Parkinson's Disease Model Mice Induced by Rotenone.Neurochemical research · 2025Article
- Chronic DSS-Induced Colitis Exacerbates Parkinson's Disease Phenotype and Its Pathological Features Following Intragastric Rotenone Exposure.ACS pharmacology & translational science · 2025Article
- Alpha-Mangostin Alleviates Mitochondrial Damage and Autophagy Dysregulation in the MPPAdvances in pharmacological and pharmaceutical sciences · 2025Article
- The Neuro-Healing Frontier: Alpha-Mangostin's Potential in Alzheimer's and Parkinson's Treatment.Combinatorial chemistry & high throughput screening · 2025Review
- Erucin, a Natural Isothiocyanate, Prevents Polyglutamine-Induced Toxicity inInternational journal of molecular sciences · 2024Article
- Recent advances in the discovery of plant-derived antimicrobial natural products to combat antimicrobial resistant pathogens: insights from 2018-2022.Natural product reports · 2023Review
- Autophagy‑regulating miRNAs: Novel therapeutic targets for Parkinson's disease (Review).International journal of molecular medicine · 2023Review
- Association of COVID-19 with Comorbidities: An Update.ACS pharmacology & translational science · 2023Review
- Extracellular vesicle‑mediated miR‑126‑3p transfer contributes to inter‑cellular communication in the liver tumor microenvironment.International journal of oncology · 2023Article
- Polyphenols: Natural food grade biomolecules for treating neurodegenerative diseases from a multi-target perspective.Frontiers in nutrition · 2023Review
- Alpha synuclein post translational modifications: potential targets for Parkinson's disease therapy?Frontiers in molecular neuroscience · 2023Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alpha-Synuclein (α-Syn) accumulation is central to the pathogenesis of Parkinson's disease (PD), hence the quest for finding potential therapeutics that may promote the α-Syn clearance is the need of the hour. To this, activation of the evolutionarily conserved protein and key regulator of the autophagy, 5'AMP-activated protein kinase (AMPK) is well-known to induce autophagy and subsequently the clearance of α-Syn aggregates. Alpha-mangostin (AM) a polyphenolic xanthone obtained from Garcinia Mangostana L. was previously reported to activate AMPK-dependent autophagy in various pre-clinical cancer models. However, no studies evidenced the effect of AM on AMPK-dependent autophagy activation in the PD. Therefore, the present study aimed to investigate the neuroprotective activity of AM in the chronic rotenone mouse model of PD against rotenone-induced α-Syn accumulation and to dissect molecular mechanisms underlying the observed neuroprotection. The findings showed that AM exerts neuroprotection against rotenone-induced α-Syn accumulation in the striatum and cortex by activating AMPK, upregulating autophagy (LC3II/I, Beclin-1), and lysosomal (TFEB) markers. Of note, an in-vitro study utilizing rat pheochromocytoma cells verified that AM conferred the neuroprotection only through AMPK activation, as the presence of inhibitors of AMPK (dorsomorphin) and autophagy (3-methyl adenine) failed to mitigate rotenone-induced α-Syn accumulation. Moreover, AM also counteracted rotenone-induced behavioral deficits, oxidative stress, and degeneration of nigro-striatal dopaminergic neurons. In conclusion, AM provided neuroprotection by ameliorating the rotenone-induced α-Syn accumulation through AMPK-dependent autophagy activation and it can be considered as a therapeutic agent which might be having a higher translational value in the treatment of PD.
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