ArticleASN neuro
Inducible HSP70 is critical in preventing the aggregation and enhancing the processing of PMP22.
Article in ASN neuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Peripheral Myelin Protein-22 and Its Prominence in Charcot-Marie-Tooth Disease.Chemical reviews · 2026Review
- Characterising PMP22-Proximal Partners in a Schwann Cell Model of Charcot-Marie-Tooth Disease Type1A.Biology · 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
- Mechanisms and treatment strategies of demyelinating and dysmyelinating Charcot-Marie-Tooth disease.Neural regeneration research · 2023Review
- 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
- Article
- Curcumin and Ethanol Effects in Trembler-J Schwann Cell Culture.Biomolecules · 2022Article
- Emerging Therapies for Charcot-Marie-Tooth Inherited Neuropathies.International journal of molecular sciences · 2021Review
- The role and therapeutic potential of Hsp90, Hsp70, and smaller heat shock proteins in peripheral and central neuropathies.Medicinal research reviews · 2021Review
- Direct relationship between increased expression and mistrafficking of the Charcot-Marie-Tooth-associated protein PMP22.The Journal of biological chemistry · 2020Article
- HSP90 Inhibitor, NVP-AUY922, Improves Myelination in Vitro and Supports the Maintenance of Myelinated Axons in Neuropathic Mice.ACS chemical neuroscience · 2019Article
- Folding and Misfolding of Human Membrane Proteins in Health and Disease: From Single Molecules to Cellular Proteostasis.Chemical reviews · 2019Article
- Elevated Peripheral Myelin Protein 22, Reduced Mitotic Potential, and Proteasome Impairment in Dermal Fibroblasts from Charcot-Marie-Tooth Disease Type 1A Patients.The American journal of pathology · 2018Article
- Targeting Heat Shock Protein 70 to Ameliorate c-Jun Expression and Improve Demyelinating Neuropathy.ACS chemical neuroscience · 2018Article
- A Novel Missense Mutation in Peripheral Myelin Protein-22 Causes Charcot-Marie-Tooth Disease.Chinese medical journal · 2017Article
- Promoting peripheral myelin repair.Experimental neurology · 2016Review
- Targeting the Diabetic Chaperome to Improve Peripheral Neuropathy.Current diabetes reports · 2016Review
- Blocking mitochondrial calcium release in Schwann cells prevents demyelinating neuropathies.The Journal of clinical investigation · 2016Article
- Promoting Neuronal Tolerance of Diabetic Stress: Modulating Molecular Chaperones.International review of neurobiology · 2016Review
- Modulating Molecular Chaperones Improves Mitochondrial Bioenergetics and Decreases the Inflammatory Transcriptome in Diabetic Sensory Neurons.ACS chemical neuroscience · 2015Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Chaperones, also called heat shock proteins (HSPs), transiently interact with proteins to aid their folding, trafficking, and degradation, thereby directly influencing the transport of newly synthesized molecules. Induction of chaperones provides a potential therapeutic approach for protein misfolding disorders, such as peripheral myelin protein 22 (PMP22)-associated peripheral neuropathies. Cytosolic aggregates of PMP22, linked with a demyelinating Schwann cell phenotype, result in suppression of proteasome activity and activation of proteostatic mechanisms, including the heat shock pathway. Although the beneficial effects of chaperones in preventing the aggregation and improving the trafficking of PMP22 have been repeatedly observed, the requirement for HSP70 in events remains elusive. In this study, we show that activation of the chaperone pathway in fibroblasts from PMP22 duplication-associated Charcot-Marie-Tooth disease type 1A patient with an FDA-approved small molecule increases HSP70 expression and attenuates proteasome dysfunction. Using cells from an HSP70.1/3(-/-) (inducible HSP70) mouse model, we demonstrate that under proteotoxic stress, this chaperone is critical in preventing the aggregation of PMP22, and this effect is aided by macroautophagy. When examined at steady-state, HSP70 appears to play a minor role in the trafficking of wild-type-PMP22, while it is crucial for preventing the buildup of the aggregation-prone Trembler-J-PMP22. HSP70 aids the processing of Trembler-J-PMP22 through the Golgi and its delivery to lysosomes via Rab7-positive vesicles. Together, these results demonstrate a key role for inducible HSP70 in aiding the processing and hindering the accumulation of misfolded PMP22, which in turn alleviates proteotoxicity within the cells.
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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.