Multiple sclerosis (MS) is an inflammatory, demyelinating neurological disease that causes severe disability. Current treatments are only partially effective, and no cure is available. This issue of the journal focuses on disease mechanisms that operate in different phases in MS—including initiation, exacerbation, remyelination and functional recovery, and progression—placing the latest findings in a clinical context, including implications for therapy.
EDITORIAL
Disease mechanisms in MS: Informing tactics to combat MS
Katie Kingwell
doi:10.1038/nrneurol.2012.218
Nature Reviews Neurology 8, 589 (2012)
RESEARCH HIGHLIGHTS
Disease mechanisms in MS: RNA profiling uncovers two distinct subsets of patients with multiple sclerosis
Heather Wood
doi:10.1038/nrneurol.2012.217
Nature Reviews Neurology 8, 591 (2012)
Disease mechanisms in MS: A role for sodium channels in regulation of macrophage-mediated pathology in multiple sclerosis lesions
Katy Malpass
doi:10.1038/nrneurol.2012.201
Nature Reviews Neurology 8, 592 (2012)
Disease mechanisms in MS: Cell adhesion molecule MCAM on pathogenic T cells—a green light for CNS entry in multiple sclerosis
Katy Malpass
doi:10.1038/nrneurol.2012.204
Nature Reviews Neurology 8, 592 (2012)
Disease mechanisms in MS: Neuronal network connectivity is altered in multiple sclerosis
Katie Kingwell
doi:10.1038/nrneurol.2012.205
Nature Reviews Neurology 8, 593 (2012)
NEWS & VIEWS
Disease mechanisms in MS: The potassium channel KIR4.1—a potential autoantigen in MS
Michael K. Racke
doi:10.1038/nrneurol.2012.193
Nature Reviews Neurology 8, 595-596 (2012)
Disease mechanisms in MS: Phases of disease improvement unrelated to relapses
Oluf Andersen
doi:10.1038/nrneurol.2012.186
Nature Reviews Neurology 8, 596-598 (2012)
REVIEWS
The initiation and prevention of multiple sclerosis
Alberto Ascherio, Kassandra L. Munger & Jan D. Lünemann
doi:10.1038/nrneurol.2012.198
Nature Reviews Neurology 8, 602-612 (2012)
Strong evidence supports the importance of genetic factors in the development of multiple sclerosis (MS), but environmental factors also have a major role. Ascherio et al. review the evidence for such factors, with a focus on three main aspects: infection with Epstein–Barr virus, vitamin D nutrition, and cigarette smoking. They discuss how these processes might influence the initiation of MS, the potential for therapeutic approaches that target these risk factors, and how lifestyle modification could aid in MS prevention.
B cells and antibodies in multiple sclerosis pathogenesis and therapy
Markus Krumbholz, Tobias Derfuss, Reinhard Hohlfeld & Edgar Meinl
doi:10.1038/nrneurol.2012.203
Nature Reviews Neurology 8, 613-623 (2012)
Increasing evidence supports a role for B cells and antibodies in the pathogenesis of multiple sclerosis (MS). Here, Meinl and colleagues discuss the proinflammatory contribution of B-cell signalling in MS, and consider potential targets of autoantibodies. The B-cell response to various MS therapies is also summarized.
Neuroprotection and repair in multiple sclerosis
Robin J. M. Franklin, Charles ffrench-Constant, Julia M. Edgar & Kenneth J. Smith
doi:10.1038/nrneurol.2012.200
Nature Reviews Neurology 8, 624-634 (2012)
In recent years, the central roles of neuronal and axonal damage, as well as axon–glial and axon–myelin interactions, in the pathogenesis and progression of multiple sclerosis (MS) have become increasingly apparent. Franklin et al. review advances in our understanding of the molecular mechanisms underlying these MS-related events, and discuss approaches towards axonal neuroprotection and repair, particularly through the regenerative process remyelination.
Neuroplasticity and functional recovery in multiple sclerosis
Valentina Tomassini, Paul M. Matthews, Alan J. Thompson, Daniel Fuglø, Jeroen J. Geurts, Heidi Johansen-Berg, Derek K. Jones, Maria A. Rocca, Richard G. Wise, Frederik Barkhof & Jacqueline Palace
doi:10.1038/nrneurol.2012.179
Nature Reviews Neurology 8, 635-646 (2012)
Despite widespread damage associated with multiple sclerosis (MS) pathology, recovery of function can occur, driven by adaptive plasticity in brain networks. Tomassini et al. review the mechanisms underlying functional recovery in MS, and discuss interventions that might promote this process. Methodological considerations for imaging neuroplasticity using functional MRI are also highlighted.
Progressive multiple sclerosis: pathology and pathogenesis
Hans Lassmann, Jack van Horssen & Don Mahad
doi:10.1038/nrneurol.2012.168
Nature Reviews Neurology 8, 647-656 (2012)
Over the past few decades, considerable progress has been made in understanding the mechanisms underlying the relapsing–remitting stage of multiple sclerosis (MS), but the disease processes that drive progressive MS remain largely unresolved. In this Review, Lassmann and colleagues explore the current state of knowledge on the pathophysiology of progressive MS, and present a pathogenetic concept for this phase of the disease that involves oxidative stress and mitochondrial injury.
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