Aquaporin-4 implicated in a form of multiple sclerosis
Sep 22, 2005 - 4:58:38 AM
Researchers have identified a molecular suspect in a disorder similar to multiple sclerosis (MS) that attacks the optic nerve and spinal cord, according to a report presented at the 130th annual meeting of the American Neurological Association in San Diego. The protein, called aquaporin-4, is a channel protein that allows water to move in and out of cells.
"Aquaporin-4 is the first specific molecule to be defined as a target for the autoimmune response in any form of MS," said author Vanda A. Lennon, MD, PhD, of the Mayo Clinic in Rochester, Minnesota. "It is also the first example of a water channel being the target of any autoimmune disorder."
Because there are many other variants of aquaporins throughout the body, Lennon suggests that these proteins might play a role in poorly understood autoimmune disorders in other organ systems.
For some time, scientists have understood that multiple sclerosis is not so much a single disease, but a category of disorders with similar damage to different parts of the nervous system. Recently, progress has been made in teasing out a particular syndrome called neuromyelitis optica (NMO), in which the body mistakenly mounts an immune attack against the optic nerve and spinal cord.
Last year, Lennon and her colleagues at Mayo, along with collaborators in Japan, were able to detect a particular antibody that occurrs in most people with NMO, but not in patients with "classical" MS.
This is particularly important for clinicians because specific treatment recommendations to help prevent blindness and other later symptoms, including paralysis, differ for NMO and MS .
In the present study, Lennon and colleagues have identified an aquaporin as the target molecule of the NMO antibody. "This finding is a departure from mainstream thinking about MS and related disorders, where the major focus of research in the past century has been the myelin that insulates nerve fibers, and the cell that manufactures myelin, known as the oligodendrocyte," said Lennon.
The Mayo Clinic group's work reveals that the protein targeted by the NMO antibody is not a component of myelin, or of oligodendrocytes. Aquaporin-4, which is the most abundant water channel in the brain, is instead located in a different type of cell called astrocytes.
"Aquaporin-4 is concentrated in membranes in the precise site where spinal cord inflammation is found in NMO patients," said Lennon.
The next step in this research is to use this knowledge to create an animal model that can be used to confirm the relationhip between aquaporin-4 and NMO, as well as to develop new and improved therapies.
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