ArticleBrain : a journal of neurology2014
The Gdap1 knockout mouse mechanistically links redox control to Charcot-Marie-Tooth disease.
Article in Brain : a journal of neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 72 citations in OpenAlex.
- Junctions in Jeopardy: the neuromuscular junction is a selective pathological target in Charcot-Marie-Tooth disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Unraveling GDAP1: Bridging Mitochondrial Biology and Peripheral Neuropathy.Biomolecules · 2026Review
- Charcot-Marie-Tooth disease and related neuropathies.Nature reviews. Disease primers · 2026Review
- Mitochondrial and peroxisomal fission in cortical neurogenesis.The international journal of biochemistry & cell biology · 2025Review
- Abnormal redox balance at membrane contact sites causes axonopathy inResearch square · 2024Article
- Extreme-Phenotype Genome-Wide Association Analysis for Growth Traits in Spotted Sea Bass (Animals : an open access journal from MDPI · 2024Article
- Amlexanox: Readthrough Induction and Nonsense-Mediated mRNA Decay Inhibition in a Charcot-Marie-Tooth Model of hiPSCs-Derived Neuronal Cells Harboring a Nonsense Mutation inPharmaceuticals (Basel, Switzerland) · 2023Article
- Rapid degeneration of iPSC-derived motor neurons lacking Gdap1 engages a mitochondrial-sustained innate immune response.Cell death discovery · 2023Article
- MiR-150 blunts cardiac dysfunction in mice with cardiomyocyte loss of βCell death discovery · 2022Article
- Quadruped Gait and Regulation of Apoptotic Factors in Tibiofemoral Joints following Intra-Articular rhPRG4 Injection inInternational journal of molecular sciences · 2022Article
- Association of Oxidative Stress with Neurological Disorders.Current neuropharmacology · 2022Article
- Effective therapeutic strategies in a preclinical mouse model of Charcot-Marie-Tooth disease.Human molecular genetics · 2021Article
- Differential hippocampal protein expression between normal mice and mice with the perioperative neurocognitive disorder: a proteomic analysis.European journal of medical research · 2021Article
- Animal Models as a Tool to Design Therapeutical Strategies for CMT-like Hereditary Neuropathies.Brain sciences · 2021Review
- Article
- GDAP1 Involvement in Mitochondrial Function and Oxidative Stress, Investigated in a Charcot-Marie-Tooth Model of hiPSCs-Derived Motor Neurons.Biomedicines · 2021Article
- The mitochondrial biogenesis signaling pathway is a potential therapeutic target for myasthenia gravis via energy metabolism (Review).Experimental and therapeutic medicine · 2021Review
- Prohibitin 1 is essential to preserve mitochondria and myelin integrity in Schwann cells.Nature communications · 2021Article
- Review
- Mitochondria-lysosome membrane contacts are defective in GDAP1-related Charcot-Marie-Tooth disease.Human molecular genetics · 2021Article
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
The ganglioside-induced differentiation-associated protein 1 (GDAP1) is a mitochondrial fission factor and mutations in GDAP1 cause Charcot-Marie-Tooth disease. We found that Gdap1 knockout mice (Gdap1(-/-)), mimicking genetic alterations of patients suffering from severe forms of Charcot-Marie-Tooth disease, develop an age-related, hypomyelinating peripheral neuropathy. Ablation of Gdap1 expression in Schwann cells recapitulates this phenotype. Additionally, intra-axonal mitochondria of peripheral neurons are larger in Gdap1(-/-) mice and mitochondrial transport is impaired in cultured sensory neurons of Gdap1(-/-) mice compared with controls. These changes in mitochondrial morphology and dynamics also influence mitochondrial biogenesis. We demonstrate that mitochondrial DNA biogenesis and content is increased in the peripheral nervous system but not in the central nervous system of Gdap1(-/-) mice compared with control littermates. In search for a molecular mechanism we turned to the paralogue of GDAP1, GDAP1L1, which is mainly expressed in the unaffected central nervous system. GDAP1L1 responds to elevated levels of oxidized glutathione by translocating from the cytosol to mitochondria, where it inserts into the mitochondrial outer membrane. This translocation is necessary to substitute for loss of GDAP1 expression. Accordingly, more GDAP1L1 was associated with mitochondria in the spinal cord of aged Gdap1(-/-) mice compared with controls. Our findings demonstrate that Charcot-Marie-Tooth disease caused by mutations in GDAP1 leads to mild, persistent oxidative stress in the peripheral nervous system, which can be compensated by GDAP1L1 in the unaffected central nervous system. We conclude that members of the GDAP1 family are responsive and protective against stress associated with increased levels of oxidized glutathione.
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