By studying gene transcripts in active lesions of multiple sclerosis via robotic sequencing and gene chips, as well as studying the very same tissue via proteomics, we have discovered several targets at the tipping points in pathophysiologic pathways controlling relapse and remission in multiple sclerosis. In this Charcot Lecture, I shall focus on osteopontin—the binding partner for alpha4 beta 1 integrin, on alpha B crystallin and on two members of the coagulation cascade tissue factor and the inhibitor of protein C. These four proteins are critical in controlling relapse and remission in MS.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Journal of the Neurological Sciences
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- The influence of the pro-inflammatory cytokine, osteopontin, on autoimmune demyelinating disease.Science. 2001; 294: 1731-1735
- Gene microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis.Nat Med. 2002; 8: 500-508
- Transcriptional analysis of targets in multiple sclerosis.Nat Rev Immunol. 2003; 3: 483-493
- Up-regulation of osteopontin and aBeta-crystallin in the normal-appearing white matter of multiple sclerosis: an immunohistochemical study utilizing tissue microarrays.Neuropathol Appl Neurobiol. Jun 2005; 31: 292-303
- Osteopontin induced relapse and progression of autoimmune brain disease via enhanced survival of activated T cells.Nat Immunol. 2007; 8: 77-86
- Elevated osteopontin levels in active relapsing–remitting multiple sclerosis.Ann Neurol. Jun 2003; 53: 819-822
- Osteopontin levels and increased disease activity in relapsing–remitting multiple sclerosis patients.J Neuroimmunol. Oct 2004; 155: 155-160
- Plasma osteopontin levels in multiple sclerosis.J Neuroimmunol. Jan 2005; 158: 231-239
- Prevention of experimental autoimmune encephalomyelitis by antibodies against a4b1 integrin.Nature. 1992; 356: 63-66
- Blocking adhesion molecules as therapy for multiple sclerosis: natalizumab.Nat Rev Drug Discovery. 2005; 4: 510-519
- The small heat-shock protein alpha B-crystallin as candidate autoantigen in multiple sclerosis.Nature. 1995; 375: 798-801
- Protective and therapeutic role for aB-crystallin in autoimmune demyelination.Nature. 2007; 448: 474-479
- Inflammatory disease: assault on the guardian.Nature. 2007; 448: 421-422
- Proteomic analysis of active multiple sclerosis lesions reveals therapeutic targets.Nature. 2008; 451: 1076-1081
- Orchestration of coagulation protease signaling by tissue factor.Trends Cardiovasc Med. 2002; 12: 149-154
- Rol' sistemy gemostaza v patogeneze i techenii rasseiannogo skleroza.Zh Nevrol Psikhiatr Im S S Korsakova (special issue 2). 2003; 103: 34-38
Accepted: June 27, 2008
Received: April 30, 2008
© 2008 Elsevier B.V. Published by Elsevier Inc. All rights reserved.