ArticleACS chemical neuroscience2021
Novologue Therapy Requires Heat Shock Protein 70 and Thioredoxin-Interacting Protein to Improve Mitochondrial Bioenergetics and Decrease Mitophagy in Diabetic Sensory Neurons.
Article in ACS chemical neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 18 citations in OpenAlex.
- Mitochondrial quality control in health and disease: Updates 2026.Chinese medical journal · 2026Review
- Endogenous Expression of HSP70 and Thioredoxin-1 During Methamphetamine-Induced Degeneration.Biomedicines · 2026Article
- Article
- 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
- Cell-Permeable HSP70 Protects Neurons and Astrocytes Against Cell Death in the Rotenone-Induced and Familial Models of Parkinson's Disease.Molecular neurobiology · 2024Article
- Investigating the interplay between mitophagy and diabetic neuropathy: Uncovering the hidden secrets of the disease pathology.Pharmacological research · 2024Review
- Sodium butyrate ameliorates high glucose-suppressed neuronal mitophagy by restoring PRKN expression via inhibiting the RELA-HDAC8 complex.Autophagy · 2024Article
- Dysfunctional Mitochondria Clearance in Situ: Mitophagy in Obesity and Diabetes-Associated Cardiometabolic Diseases.Diabetes & metabolism journal · 2024Review
- Cell metabolism pathways involved in the pathophysiological changes of diabetic peripheral neuropathy.Neural regeneration research · 2024Review
- Myocardial Glutathione Synthase and TRXIP Expression Are Significantly Elevated in Hypertension and Diabetes: Influence of Stress on Antioxidant Pathways.Pathophysiology : the official journal of the International Society for Pathophysiology · 2023Article
- IGF-1 Microinjection in the Prefrontal Cortex Attenuates Fentanyl-Seeking Behavior in Mice.The international journal of neuropsychopharmacology · 2023Article
- 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
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Diabetic peripheral neuropathy (DPN) is a complication of diabetes whose pathophysiology is linked to altered mitochondrial bioenergetics (mtBE). KU-596 is a small molecule neurotherapeutic that reverses symptoms of DPN, improves sensory neuron mtBE, and decreases the pro-oxidant protein, thioredoxin-interacting protein (Txnip) in a heat shock protein 70 (Hsp70)-dependent manner. However, the mechanism by which KU-596 improves mtBE and the role of Txnip in drug efficacy remains unknown. Mitophagy is a quality-control mechanism that selectively targets damaged mitochondria for degradation. The goal of this study was to determine if KU-596 therapy improved DPN, mtBE, and mitophagy in an Hsp70- and Txnip-dependent manner. Mito-QC (MQC) mice express a mitochondrially targeted mCherry-GFP fusion protein that enables visualizing mitophagy. Diabetic MQC, MQC × Hsp70 knockout (KO), and MQC × Txnip KO mice developed sensory and nerve conduction dysfunctions consistent with the onset of DPN. KU-596 therapy improved these measures, and this was dependent on Hsp70 but not Txnip. In MQC mice, diabetes decreased mtBE and increased mitophagy and KU-596 treatment reversed these effects. In contrast, KU-596 was unable to improve mtBE and decrease mitophagy in MQC × Hsp70 and MQC × Txnip KO mice. These data suggest that Txnip is not necessary for the development of the sensory symptoms and mitochondrial dysfunction induced by diabetes. KU-596 therapy may improve mitochondrial tolerance to diabetic stress to decrease mitophagic clearance in an Hsp70- and Txnip-dependent manner.
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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.