ArticleThe Journal of pharmacology and experimental therapeutics2014
Heat shock protein 70 is necessary to improve mitochondrial bioenergetics and reverse diabetic sensory neuropathy following KU-32 therapy.
Article in The Journal of pharmacology and experimental therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Ferroptosis and ferritinophagy in diabetes complications.Molecular metabolism · 2022Pooled it
- Redox and bioenergetic modulation by plumbagin attenuated neuropathic allodynia in mice with diet-induced diabetes.Nutrition & diabetes · 2026Article
- Total Reversal of ALS Confirmed by EMG Normalization, Structural Reconstitution, and Neuromuscular-Molecular Restoration Achieved Through Computerized Brain-Guided Reengineering of the 1927 Nobel Prize Fever Therapy: A Case Report.Diseases (Basel, Switzerland) · 2025Article
- Redox and Bioenergetic Modulation by Acacetin Attenuated Neuropathic Allodynia in Mice with Diet-induced Diabetes.Molecular neurobiology · 2025Article
- Beyond Folding: Expanding the Functional Landscape of Hsp90 Chaperone Machinery in Health and Disease.International journal of molecular sciences · 2025Review
- Muscarinic Receptor Antagonism and TRPM3 Activation as Stimulators of Mitochondrial Function and Axonal Repair in Diabetic Sensorimotor Polyneuropathy.International journal of molecular sciences · 2025Review
- Schwann Cell Protein Kinase RNA-like ER Kinase (PERK) Is Not Necessary for the Development of Diabetic Peripheral Neuropathy but Negates the Efficacy of Cemdomespib Therapy.ACS pharmacology & translational science · 2025Article
- Cemdomespib Therapy Slows the Progression of Neuromuscular Weakness and Demyelination in the R75W-Connexin 32 Animal Model of Charcot-Marie-Tooth 1X Disease.ACS pharmacology & translational science · 2025Article
- How inflammation dictates diabetic peripheral neuropathy: An enlightening review.CNS neuroscience & therapeutics · 2024Review
- Pharmacologic Targeting of the C-Terminus of Heat Shock Protein 90 Improves Neuromuscular Function in Animal Models of Charcot Marie Tooth X1 Disease.ACS pharmacology & translational science · 2023Article
- Impact of gut-peripheral nervous system axis on the development of diabetic neuropathy.Memorias do Instituto Oswaldo Cruz · 2023Article
- Protection against Aβ-induced neuronal damage by KU-32: PDHK1 inhibition as important target.Frontiers in aging neuroscience · 2023Article
- Potential Roles of Anti-Inflammatory Plant-Derived Bioactive Compounds Targeting Inflammation in Microvascular Complications of Diabetes.Molecules (Basel, Switzerland) · 2022Review
- Sensory neuron dysfunction in orthotopic mouse models of colon cancer.Journal of neuroinflammation · 2022Article
- Neurobiological Opportunities in Diabetic Polyneuropathy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Novologue Therapy Requires Heat Shock Protein 70 and Thioredoxin-Interacting Protein to Improve Mitochondrial Bioenergetics and Decrease Mitophagy in Diabetic Sensory Neurons.ACS chemical neuroscience · 2021Article
- Sensory neurons derived from diabetic rats exhibit deficits in functional glycolysis and ATP that are ameliorated by IGF-1.Molecular metabolism · 2021Article
- The role and therapeutic potential of Hsp90, Hsp70, and smaller heat shock proteins in peripheral and central neuropathies.Medicinal research reviews · 2021Review
- Muscarinic Toxin 7 Signals Via CaMolecular neurobiology · 2020Article
- Evolving concepts on the role of dyslipidemia, bioenergetics, and inflammation in the pathogenesis and treatment of diabetic peripheral neuropathy.Journal of the peripheral nervous system : JPNS · 2020Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Impaired neuronal mitochondrial bioenergetics contributes to the pathophysiologic progression of diabetic peripheral neuropathy (DPN) and may be a focal point for disease management. We have demonstrated that modulating heat shock protein (Hsp) 90 and Hsp70 with the small-molecule drug KU-32 ameliorates psychosensory, electrophysiologic, morphologic, and bioenergetic deficits of DPN in animal models of type 1 diabetes. The current study used mouse models of type 1 and type 2 diabetes to determine the relationship of changes in sensory neuron mitochondrial bioenergetics to the onset of and recovery from DPN. The onset of DPN showed a tight temporal correlation with a decrease in mitochondrial bioenergetics in a genetic model of type 2 diabetes. In contrast, sensory hypoalgesia developed 10 weeks before the occurrence of significant declines in sensory neuron mitochondrial bioenergetics in the type 1 model. KU-32 therapy improved mitochondrial bioenergetics in both the type 1 and type 2 models, and this tightly correlated with a decrease in DPN. Mechanistically, improved mitochondrial function following KU-32 therapy required Hsp70, since the drug was ineffective in diabetic Hsp70 knockout mice. Our data indicate that changes in mitochondrial bioenergetics may rapidly contribute to nerve dysfunction in type 2 diabetes, but not type 1 diabetes, and that modulating Hsp70 offers an effective approach toward correcting sensory neuron bioenergetic deficits and DPN in both type 1 and type 2 diabetes.
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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.