Brain connexins in demyelinating diseases: therapeutic potential of glial targets.
Several demyelinating syndromes have been linked to mutations in glial gap junction proteins, the connexins. Although mutations in connexins of the myelinating cells, Schwann cells and oligodendrocytes, were initially described, recent data have shown that astrocytes also play a major role in the demyelination process. Alterations in astrocytic proteins directly affect the oligodendrocytes' ability to maintain myelin structure, and associated astrocytic proteins that regulate water and ionic fluxes, including aquaporins, can also regulate myelin integrity. Here, we will review the main evidence from human disorders and transgenic mouse models that implicate glial gap junction proteins in demyelinating diseases and the therapeutic potential of some of these targets. This article is part of a Special Issue entitled Electrical Synapses.
Division of Glia Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester Medical School, Rochester, NY 14640, USA. Marisa_Cotrina@URMC.Rochester.edu
Maria Luisa
ML
Cotrina
Maiken
M
Nedergaard
D000818:Animals; D051401:Aquaporin 4 / Q000502:physiology; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D017630:Connexins / Q000235:genetics / Q000502:physiology*; D003711:Demyelinating Diseases / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D051379:Mice; D009457:Neuroglia / Q000187:drug effects*; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology; D011188:Potassium / Q000502:physiology
D051401:Aquaporin 4; D017630:Connexins; D011188:Potassium