ArticleThe Journal of biological chemistry2013
A blood-brain barrier (BBB) disrupter is also a potent α-synuclein (α-syn) aggregation inhibitor: a novel dual mechanism of mannitol for the treatment of Parkinson disease (PD).
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 104 citations in OpenAlex.
- miR126-mediated alteration of vascular integrity in Rett syndrome.Molecular psychiatry · 2026Article
- Mutational Scanning of α-Synuclein using a Clickable Protein Tag Reveals Determinants of Membrane-Induced Aggregation.bioRxiv : the preprint server for biology · 2026Article
- Silicon quantum dots for neurotheranostic applications in dopamine detection.Journal of nanobiotechnology · 2026Review
- Antibacterial microcins self-assemble to promote biofilm formation in Acinetobacter baumannii.Cell reports · 2026Article
- "Proteinjury": a universal pathological mechanism mediated by cerebrospinal fluid in neurodegeneration and trauma.Frontiers in cell and developmental biology · 2025Review
- Liquid-liquid phase separation of α-synuclein is highly sensitive to sequence complexity.Protein science : a publication of the Protein Society · 2024Article
- Entrepreneurial treatment activism for undone science: mannitol and Parkinson's disease.BioSocieties · 2023Article
- HMGB1 is a Potential and Challenging Therapeutic Target for Parkinson's Disease.Cellular and molecular neurobiology · 2023Review
- Proteinopathies: Deciphering Physiology and Mechanisms to Develop Effective Therapies for Neurodegenerative Diseases.Molecular neurobiology · 2022Review
- Cavitation Feedback Control of Focused Ultrasound Blood-Brain Barrier Opening for Drug Delivery in Patients with Parkinson's Disease.Pharmaceutics · 2022Article
- Anti-Parkinsonian Therapy: Strategies for Crossing the Blood-Brain Barrier and Nano-Biological Effects of Nanomaterials.Nano-micro letters · 2022Review
- Addressing Blood-Brain Barrier Impairment in Alzheimer's Disease.Biomedicines · 2022Review
- Propagation of tau and α-synuclein in the brain: therapeutic potential of the glymphatic system.Translational neurodegeneration · 2022Review
- Shared Molecular Targets in Parkinson's Disease and Arterial Hypertension: A Systematic Review.Biomedicines · 2022Review
- Why Should Natural Principles Be Simple?Philosophia (Ramat-Gan, Israel) · 2022Article
- Alpha-Synuclein Targeting Therapeutics for Parkinson's Disease and Related Synucleinopathies.Frontiers in neurology · 2022Review
- Polymorphism in alpha-synuclein oligomers and its implications in toxicity under disease conditions.Frontiers in molecular biosciences · 2022Review
- GPR40 Agonist Ameliorate Pathological Neuroinflammation of Alzheimer's Disease via the Modulation of Gut Microbiota and Immune System, a Mini-Review.Neurotoxicity research · 2021Review
- Cerebral dopamine neurotrophic factor reduces α-synuclein aggregation and propagation and alleviates behavioral alterations in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Safety and Tolerability, Dose-Escalating, Double-Blind Trial of Oral Mannitol in Parkinson's Disease.Frontiers in neurology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
The development of disease-modifying therapy for Parkinson disease has been a main drug development challenge, including the need to deliver the therapeutic agents to the brain. Here, we examined the ability of mannitol to interfere with the aggregation process of α-synuclein in vitro and in vivo in addition to its blood-brain barrier-disrupting properties. Using in vitro studies, we demonstrated the effect of mannitol on α-synuclein aggregation. Although low concentration of mannitol inhibited the formation of fibrils, high concentration significantly decreased the formation of tetramers and high molecular weight oligomers and shifted the secondary structure of α-synuclein from α-helical to a different structure, suggesting alternative potential pathways for aggregation. When administered to a Parkinson Drosophila model, mannitol dramatically corrected its behavioral defects and reduced the amount of α-synuclein aggregates in the brains of treated flies. In the mThy1-human α-synuclein transgenic mouse model, a decrease in α-synuclein accumulation was detected in several brain regions following treatment, suggesting that mannitol promotes α-synuclein clearance in the cell bodies. It appears that mannitol has a general neuroprotective effect in the transgenic treated mice, which includes the dopaminergic system. We therefore suggest mannitol as a basis for a dual mechanism therapeutic agent for the treatment of Parkinson disease.
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