Insights Into the Molecular Pathogenesis of Progression in Multiple Sclerosis
Potential Implications for Future Therapies
Jaime Imitola, MD;
Tanuja Chitnis, MD;
Samia J. Khoury, MD
Arch Neurol. 2006;63:25-33.
Despite recent advances in the diagnosis and treatment of multiple sclerosis, we still lack a consensus regarding the causes, pathogenesis, and mechanisms of disease progression. Current evidence indicates that multiple sclerosis is an inflammatory neurodegenerative disorder in which both adaptive and innate immunity play important roles in initiation and maintenance of the disease. Recent evidence supports the notion of molecular pathologic abnormalities beyond the plaques and dysfunction of neurons in normal appearing areas, in addition to the multifocal demyelination and axonal loss, as important features that may underlie early reversible changes in the disease. Chronic failure of remyelination, axonal regeneration, and neuronal dysfunction may contribute to disease progression. This article discusses the emerging molecular evidence for the progression of multiple sclerosis with particular focus on alterations in the local central nervous system microenvironment of neural and glial cells. The molecular pathways leading to structural and functional neurodegeneration and those that prevent regeneration need to be identified in order to design new therapeutic strategies that can halt or even reverse disease progression.
Author Affiliations: Center for Neurologic Diseases and Partners Multiple Sclerosis Center, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Axonal loss in the retinal nerve fiber layer in patients with multiple sclerosis
Pueyo et al.
Mult Scler 2008;14:609-614.
ABSTRACT
Natural history of secondary-progressive multiple sclerosis
Tremlett et al.
Mult Scler 2008;14:314-324.
ABSTRACT
Myeloperoxidase-targeted imaging of active inflammatory lesions in murine experimental autoimmune encephalomyelitis
Chen et al.
Brain 2008;131:1123-1133.
ABSTRACT
| FULL TEXT
Persistent activation of microglia is associated with neuronal dysfunction of callosal projecting pathways and multiple sclerosis-like lesions in relapsing remitting experimental autoimmune encephalomyelitis
Rasmussen et al.
Brain 2007;130:2816-2829.
ABSTRACT
| FULL TEXT
What Causes Multiple Sclerosis to Worsen?
Phillips
Arch Neurol 2007;64:167-168.
FULL TEXT
Innate Immunity in Multiple Sclerosis: Myeloid Dendritic Cells in Secondary Progressive Multiple Sclerosis Are Activated and Drive a Proinflammatory Immune Response
Karni et al.
J. Immunol. 2006;177:4196-4202.
ABSTRACT
| FULL TEXT
|
