ArticlePloS one2014
Chronic treatment with novel small molecule Hsp90 inhibitors rescues striatal dopamine levels but not α-synuclein-induced neuronal cell loss.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- From synaptic development to degeneration: a narrative review of small molecule strategies targeting alpha-synuclein in Parkinson's disease.Metabolic brain disease · 2026Review
- Scyllo-Inositol as a Neuroactive Agent: From Pharmacokinetics to Neuroprotective and Antiepileptic Effects.Nutrients · 2026Review
- Beyond Folding: Expanding the Functional Landscape of Hsp90 Chaperone Machinery in Health and Disease.International journal of molecular sciences · 2025Review
- Review
- In Vivo Visualization and Quantification of Brain Heat Shock Protein 90 with [Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025Article
- Molecular Docking, Bioinformatic Analysis, and Experimental Verification for the Effect of Naringin on ADHD: Possible Inhibition of GSK-3β and HSP90.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Fibrillar Alpha-Synuclein Alters the Intracellular Chaperone Levels within Hours of Its Internalization.ACS omega · 2024Article
- Heat Shock Response and Heat Shock Proteins: Current Understanding and Future Opportunities in Human Diseases.International journal of molecular sciences · 2024Review
- Assessment of the Anti-Amyloidogenic Properties of Essential Oils and Their Constituents in Cells Using a Whole-Cell Recombinant Biosensor.Brain sciences · 2023Article
- Modulating Stress Proteins in Response to Therapeutic Interventions for Parkinson's Disease.International journal of molecular sciences · 2023Review
- Six Decades of Dopamine Hypothesis: Is Aryl Hydrocarbon Receptor the New D2?Reports (MDPI) · 2023Review
- Inhibition of Protein Aggregation and Endoplasmic Reticulum Stress as a Targeted Therapy for α-Synucleinopathy.Pharmaceutics · 2023Review
- Quinones as Neuroprotective Agents.Antioxidants (Basel, Switzerland) · 2023Review
- The Role of Pathogens and Anti-Infective Agents in Parkinson's Disease, from Etiology to Therapeutic Implications.Journal of Parkinson's disease · 2022Review
- Adeno-Associated Viral Vectors as Versatile Tools for Parkinson's Research, Both for Disease Modeling Purposes and for Therapeutic Uses.International journal of molecular sciences · 2021Review
- Pharmacological induction of heat shock proteins ameliorates toxicity of mutant PKCγ in spinocerebellar ataxia type 14.The Journal of biological chemistry · 2018Article
- Hsp90 Co-chaperone p23 contributes to dopaminergic mitochondrial stress via stabilization of PHD2: Implications for Parkinson's disease.Neurotoxicology · 2018Article
- Alpha-synuclein oligomers: a new hope.Acta neuropathologica · 2017Review
- Possible Function of Molecular Chaperones in Diseases Caused by Propagating Amyloid Aggregates.Frontiers in neuroscience · 2017Review
- Cellular selectivity of AAV serotypes for gene delivery in neurons and astrocytes by neonatal intracerebroventricular injection.PloS one · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 7 institutions in 2 countries.
Funding
Abstract
Hsp90 inhibitors such as geldanamycin potently induce Hsp70 and reduce cytotoxicity due to α-synuclein expression, although their use has been limited due to toxicity, brain permeability, and drug design. We recently described the effects of a novel class of potent, small molecule Hsp90 inhibitors in cells overexpressing α-synuclein. Screening yielded several candidate compounds that significantly reduced α-synuclein oligomer formation and cytotoxicity associated with Hsp70 induction. In this study we examined whether chronic treatment with candidate Hsp90 inhibitors could protect against α-synuclein toxicity in a rat model of parkinsonism. Rats were injected unilaterally in the substantia nigra with AAV8 expressing human α-synuclein and then treated with drug for approximately 8 weeks by oral gavage. Chronic treatment with SNX-0723 or the more potent, SNX-9114 failed to reduce dopaminergic toxicity in the substantia nigra compared to vehicle. However, SNX-9114 significantly increased striatal dopamine content suggesting a positive neuromodulatory effect on striatal terminals. Treatment was generally well tolerated, but higher dose SNX-0723 (6-10 mg/kg) resulted in systemic toxicity, weight loss, and early death. Although still limited by potential toxicity, Hsp90 inhibitors tested herein demonstrate oral efficacy and possible beneficial effects on dopamine production in a vertebrate model of parkinsonism that warrant further study.
Indexed as
Identifiers
What OpenQuestion holds
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.