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Axonal Charcot-Marie-Tooth Disease: from Common Pathogenic Mechanisms to Emerging Treatment Opportunities
- Source :
- Neurotherapeutics
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Inherited peripheral neuropathies are a genetically and phenotypically diverse group of disorders that lead to degeneration of peripheral neurons with resulting sensory and motor dysfunction. Genetic neuropathies that primarily cause axonal degeneration, as opposed to demyelination, are most often classified as Charcot-Marie-Tooth disease type 2 (CMT2) and are the focus of this review. Gene identification efforts over the past three decades have dramatically expanded the genetic landscape of CMT and revealed several common pathological mechanisms among various forms of the disease. In some cases, identification of the precise genetic defect and/or the downstream pathological consequences of disease mutations have yielded promising therapeutic opportunities. In this review, we discuss evidence for pathogenic overlap among multiple forms of inherited neuropathy, highlighting genetic defects in axonal transport, mitochondrial dynamics, organelle-organelle contacts, and local axonal protein translation as recurrent pathological processes in inherited axonal neuropathies. We also discuss how these insights have informed emerging treatment strategies, including specific approaches for single forms of neuropathy, as well as more general approaches that have the potential to treat multiple types of neuropathy. Such therapeutic opportunities, made possible by improved understanding of molecular and cellular pathogenesis and advances in gene therapy technologies, herald a new and exciting phase in inherited peripheral neuropathy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-021-01099-2.
- Subjects :
- Pharmacology
medicine.medical_specialty
Neurology
business.industry
Genetic enhancement
Review
Disease
medicine.disease
Axonal Transport
Axons
Pathogenesis
Peripheral neuropathy
Charcot-Marie-Tooth Disease
Mutation
Axoplasmic transport
Humans
Medicine
Pharmacology (medical)
Identification (biology)
Neurology (clinical)
business
Neuroscience
Pathological
Subjects
Details
- ISSN :
- 18787479 and 19337213
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Neurotherapeutics
- Accession number :
- edsair.doi.dedup.....e8ca9c091b08da11ddf003d1ebcf27a6
- Full Text :
- https://doi.org/10.1007/s13311-021-01099-2