ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2014
A GCase chaperone improves motor function in a mouse model of synucleinopathy.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 106 citations in OpenAlex.
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- Molecular mirror: reflecting the complexity of Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Pharmacological inhibition of O-GlcNAcase reduces pS129-α-synuclein positive aggregates in the substantia nigra of mThy1-hSNCA mice.Journal of Parkinson's disease · 2026Article
- Metabolic reprogramming and altered ATP content impair neuroprotective functions of microglia in β-glucocerebrosidase deficiency models.Journal of neuroinflammation · 2025Article
- An injectable hydrogel containingRSC advances · 2025Article
- Synaptic and cognitive impairment associated with L444P heterozygous glucocerebrosidase mutation.Brain : a journal of neurology · 2025Article
- Advances in autophagy for Parkinson's disease pathogenesis and treatment.Ageing and neurodegenerative diseases · 2025Article
- Mitochondrial dysfunction, cause or consequence in neurodegenerative diseases?BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- High-throughput screening for small-molecule stabilizers of misfolded glucocerebrosidase in Gaucher disease and Parkinson's disease.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Lysosomal dysfunction in α-synuclein pathology: molecular mechanisms and therapeutic strategies.Cellular and molecular life sciences : CMLS · 2024Review
- Development of quantitative high-throughput screening assays to identify, validate, and optimize small-molecule stabilizers of misfolded β-glucocerebrosidase with therapeutic potential for Gaucher disease and Parkinson's disease.bioRxiv : the preprint server for biology · 2024Article
- Herbal/Natural Compounds Resist Hallmarks of Brain Aging: From Molecular Mechanisms to Therapeutic Strategies.Antioxidants (Basel, Switzerland) · 2023Review
- A Mouse Model to Test Novel Therapeutics for Parkinson's Disease: an Update on the Thy1-aSyn ("line 61") Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- Role of rodent models in advancing precision medicine for Parkinson's disease.Handbook of clinical neurology · 2023Review
- Precision Medicine in Parkinson's Disease: From Genetic Risk Signals to Personalized Therapy.Brain sciences · 2022Review
- Article
- GCase Enhancers: A Potential Therapeutic Option for Gaucher Disease and Other Neurological Disorders.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Microgliosis and neuronal proteinopathy in brain persist beyond viral clearance in SARS-CoV-2 hamster model.EBioMedicine · 2022Article
- Review
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
Abstract
Mutation of the lysosomal hydrolase acid-β-glucosidase (GCase), which leads to reduced GCase activity, is one of the most frequent genetic risk factors for Parkinson's disease (PD) and promotes α-synuclein accumulation in the brain, a hallmark of PD and other synucleinopathies. Whether targeting GCase pharmacologically is a valid therapeutic strategy for sporadic PD in the absence of GCase mutation is unknown. We have investigated whether increasing the stability, trafficking, and activity of wild-type GCase could be beneficial in synucleinopathies by administering the pharmacological chaperone AT2101 (afegostat-tartrate, isofagomine) to mice that overexpress human wild-type α-synuclein (Thy1-aSyn mice). AT2101 administered orally for 4 months to Thy1-aSyn mice improved motor and nonmotor function, abolished microglial inflammatory response in the substantia nigra, reduced α-synuclein immunoreactivity in nigral dopaminergic neurons, and reduced the number of small α-synuclein aggregates, while increasing the number of large α-synuclein aggregates. These data support the further investigation of pharmacological chaperones that target GCase as a therapeutic approach for sporadic PD and other synucleinopathies, even in the absence of glucocerebrosidase mutations.
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