ArticleHuman molecular genetics2017
Mitochondrial deficits and abnormal mitochondrial retrograde axonal transport play a role in the pathogenesis of mutant Hsp27-induced Charcot Marie Tooth Disease.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- Mitochondrial dysfunction, metabolic quiescence and premature senescence in CMT4B3 fibroblasts.Human molecular genetics · 2026Article
- Review
- Hereditary Polyneuropathies in the Era of Precision Medicine: Genetic Complexity and Emerging Strategies.Genes · 2026Review
- Charcot Marie Tooth disease pathology is associated with mitochondrial dysfunction and lower glutathione production.Cellular and molecular life sciences : CMLS · 2025Article
- A Case Report and Literature Review of Charcot-Marie-Tooth Disease Type 2F in a Family.Degenerative neurological and neuromuscular disease · 2025Article
- High Content Analysis of Mitochondrial Function in Induced Pluripotent Stem Cell-Derived Neurons.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Advances and challenges in modeling inherited peripheral neuropathies using iPSCs.Experimental & molecular medicine · 2024Review
- Disruption of axonal transport in neurodegeneration.The Journal of clinical investigation · 2023Review
- Small heat shock proteins operate as molecular chaperones in the mitochondrial intermembrane space.Nature cell biology · 2023Article
- Abnormal Intraepidermal Nerve Fiber Density in Disease: A Scoping Review.medRxiv : the preprint server for health sciences · 2023Article
- Alleviative effects of pinostrobin against cadmium-induced renal toxicity in rats by reducing oxidative stress, apoptosis, inflammation, and mitochondrial dysfunction.Frontiers in nutrition · 2023Article
- Abnormal intraepidermal nerve fiber density in disease: A scoping review.Frontiers in neurology · 2023Article
- Impaired interactions of ataxin-3 with protein complexes reveals their specific structure and functions in SCA3 Ki150 model.Frontiers in molecular neuroscience · 2023Article
- Heterogeneous Clinical Phenotypes of dHMN Caused by Mutation inBiomolecules · 2022Article
- Article
- Insights on Human Small Heat Shock Proteins and Their Alterations in Diseases.Frontiers in molecular biosciences · 2022Review
- Insights Into the Role of Heat Shock Protein 27 in the Development of Neurodegeneration.Frontiers in molecular neuroscience · 2022Review
- Quantifying mitochondrial volume density in phrenic motor neurons.Journal of neuroscience methods · 2021Article
- Held Up in Traffic-Defects in the Trafficking Machinery in Charcot-Marie-Tooth Disease.Frontiers in molecular neuroscience · 2021Review
- Intra-axonal mechanisms driving axon regeneration.Brain research · 2020Review
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Mutations in the small heat shock protein Hsp27, encoded by the HSPB1 gene, have been shown to cause Charcot Marie Tooth Disease type 2 (CMT-2) or distal hereditary motor neuropathy (dHMN). Protein aggregation and axonal transport deficits have been implicated in the disease. In this study, we conducted analysis of bidirectional movements of mitochondria in primary motor neuron axons expressing wild type and mutant Hsp27. We found significantly slower retrograde transport of mitochondria in Ser135Phe, Pro39Leu and Arg140Gly mutant Hsp27 expressing motor neurons than in wild type Hsp27 neurons, although anterograde movement velocities remained normal. Retrograde transport of other important cargoes, such as the p75 neurotrophic factor receptor was minimally altered in mutant Hsp27 neurons, implicating that axonal transport deficits primarily affect mitochondria and the axonal transport machinery itself is less affected. Investigation of mitochondrial function revealed a decrease in mitochondrial membrane potential in mutant Hsp27 expressing motor axons, as well as a reduction in mitochondrial complex 1 activity, increased vulnerability of mitochondria to mitochondrial stressors, leading to elevated superoxide release and reduced mitochondrial glutathione (GSH) levels, although cytosolic GSH remained normal. This mitochondrial redox imbalance in mutant Hsp27 motor neurons is likely to cause low level of oxidative stress, which in turn will contribute to, and indeed may be the underlying cause of the deficits in mitochondrial axonal transport. Together, these findings suggest that the mitochondrial abnormalities in mutant Hsp27-induced neuropathies may be a primary cause of pathology, leading to further deficits in the mitochondrial axonal transport and onset of disease.
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