Too Much Of A Charge-Switching Enzyme Causes Symptoms Of Multiple Sclerosis And Related Disorders In Mouse Models

Main Category: Multiple Sclerosis
Also Included In: Neurology / Neuroscience;  Biology / Biochemistry
Article Date: 06 Nov 2008 - 2:00 PDT

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A new study highlights the role of a charge-switching enzyme in nervous system deficits characteristic of multiple sclerosis and other related neurological illness.

Multiple sclerosis (MS) is one of several diseases in which myelin - the insulator for electrical signaling in the nervous system - breaks down and causes severe deficits in brain and nerve function. Much like the rubber insulation on an electrical cord, myelin surrounds long projections from the body of a neuron, and allows signals to travel down the cell with speed and efficiency. Patients with MS and other "de-myelinating" diseases therefore suffer deficits in balance, coordination, and movement, as well as sensory disturbances, from the loss of this neuronal insulation.

A major research initiative in treating these diseases is identifying the molecular factors and changes that lead to myelin breakdown. In a new study published in Disease Models & Mechanisms (DMM), http://dmm.biologists.org/, a team of Canadian researchers report on a new mouse model of disease which will help in understanding how demyelination occurs. Previous research had identified that an enzyme known as peptidylarginine deiminase 2, or PAD2, is increased in patients with MS, and that PAD2 switches a charge on a protein key to myelin stability. Therefore, Abdiwahab A. Musse and colleagues at the University of Guelph and the Hospital for Sick Children in Ontario created a genetically modified mouse expressing too much of an enzyme known as PAD2. They found that these mice had significant loss of myelin, and also have behavioral deficits, such as abnormal movement, balance, and coordination.

Not only does this work present a new mouse model to study demyleinating disease, but it also stresses the importance of PAD in maintaining myelin integrity. Their work highlights PAD as a potential therapeutic target, as well as a potential marker for early detection of MS and other diseases characterized by a loss of myelin.

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Commentary on this work by researchers Mario Moscarello and Fabrizio Mastronardi will be featured in the DMM Podcast for issue 4/5 of DMM. Podcasts are available via the DMM website at: http://dmm.biologists.org>dmm.biologists.org/.

The report was written by Abdiwahab A. Musse, Dorothee Bienzle, Roberto Poma, and George Harauz at the University of Guelph in Guelph, Ontario, and Zhen Li, Cameron A. Ackerley, Helena Lei, Mario A. Moscarello and Fabrizio G. Mastronardi at the Hospital for Sick Children in Toronto, Ontario. The report is published in the November/December issue of a new research journal, Disease Models & Mechanisms (DMM), published by The Company of Biologists, a non-profit based in Cambridge, UK.

About Disease Models & Mechanisms:

Disease Models & Mechanisms (DMM) is a new research journal publishing both primary scientific research, as well as review articles, editorials, and research highlights. The journal's mission is to provide a forum for clinicians and scientists to discuss basic science and clinical research related to human disease, disease detection and novel therapies. DMM is published by the Company of Biologists, a non-profit organization based in Cambridge, UK.

The Company also publishes the international biology research journals Development, Journal of Cell Science, and The Journal of Experimental Biology. In addition to financing these journals, the Company provides grants to scientific societies and supports other activities including travelling fellowships for junior scientists, workshops and conferences. The world's poorest nations receive free and unrestricted access to the Company's journals.

Source: Donna Perry
The Company of Biologists

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