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Dynamin-2 in nervous system disorders

Journal

JOURNAL OF NEUROCHEMISTRY
Volume 128, Issue 2, Pages 210-223

Publisher

WILEY
DOI: 10.1111/jnc.12455

Keywords

Alzheimer's disease; centronuclear myopathy; Charcot-Marie-Tooth neuropathy; cytoskeleton; dynamin-2; vesicles trafficking

Funding

  1. Fondos ICM-ECONOMIA Project (Chile) [P09-022-F]

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Dynamin-2 is a pleiotropic GTPase whose best-known function is related to membrane scission during vesicle budding from the plasma or Golgi membranes. In the nervous system, dynamin-2 participates in synaptic vesicle recycling, post-synaptic receptor internalization, neurosecretion, and neuronal process extension. Some of these functions are shared with the other two dynamin isoforms. However, the involvement of dynamin-2 in neurological illnesses points to a critical function of this isoform in the nervous system. In this regard, mutations in the dynamin-2 gene results in two congenital neuromuscular disorders. One of them, Charcot-Marie-Tooth disease, affects myelination and peripheral nerve conduction, whereas the other, Centronuclear Myopathy, is characterized by a progressive and generalized atrophy of skeletal muscles, yet it is also associated with abnormalities in the nervous system. Furthermore, single nucleotide polymorphisms located in the dynamin-2 gene have been associated with sporadic Alzheimer's disease. In the present review, we discuss the pathogenic mechanisms implicated in these neurological disorders.

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