Multiple sclerosis

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Please have patience as I edit this page over the next week! Thank you!--Kirsten Eldredge 04:06, 21 April 2012 (IDT)

Multiple sclerosis (MS)- an autoimmune disease that effects every patient differently based on the neurologic lesions found throughout the body. While some can go through their lives with relatively mild symptoms and short periods of relapse, others can become incapacitated within years or even months. Defined by Nylander and Hafler, MS is a "multifocal demyelinating disease with progressive neurodegeneration caused by an autoimmune response to self-antigens in a genetically susceptible individual."^[1] While the effects of the disease are well known, and various treatments exist for the disease, the exact identity of an antigen or infectious agent that causes the initiation of a myriad of symptoms is unknown.

There are three ways in which MS is categorized: relapsing-remitting (RRMS), secondary progressive (SPMS), and primary progressive (PPMS). In RRMS, the patient experiences periods of time in which the symptoms considerably increase, although the neurological function of the patient usually returns to normal after the episode. Those with SPMS have symptoms like RRMS, but do not return to normal neurological function after the episode, rather they sustain the neurological damage (such as permanently losing the use of an arm). In PPMS, the patient has an initial episode that never ends. That is, once the symptoms begin, there is no relapse in the neurological degradation. Rather, a constant autoimmune attack on the patient's body causes increasingly severe symptoms, and sometimes death.

spinqualitylabelsall models Click on the green links to the left to see key structural features of Interferon Beta (PDB entry 1ifa) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Pathology Many antigens have been investigated to determine whether they are the cause of T cell problems including: (MBP, 1bx2) with a peptide shown; (PLP, 2xpg) with peptide shown; (MOG, 3csp); oligodendroglia-specific enzyme transaldolase, and heat shock protein alphabeta-crystallin. Interferon-β Interferon-β is a protein growth factor that stimulates an antiviral defense. Its encoding gene is one of only two known vertebrate structural genes that lacks introns.[2] Interferon-β is a relatively simple biological response modifier, with several . It consists of five , as well as multiple interconnecting . Helices A, B and D run , and helices C and E run to the other three helices, but to one another. Helix A consists of residues 6-23; Helix B consists of residues 49-65; Helix C consists of residues 77-91; Helix D consists of residues 112-131; and Helix E consists of residues 135-155.[3][4] Interferons alpha and beta interact with a receptor at the surface of [5] Interferon receptor [6] Interferon receptor bound to interferon alpha A comparison of Interferon Alpha to Interferon Beta spinqualitylabelsall models Interferon Alpha Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image spinqualitylabelsall models Interferon Beta Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Other Treatments

Interesting discoveries have been made on possible inhibitors of myelin repair functions within the body, with an obvious application to MS treatment. This The structure of the is a module implicated in central nervous system repair inhibition.

Copaxone

References

1. ↑ Nylander A, Hafler DA. Multiple sclerosis. J Clin Invest. 2012 Apr 2;122(4):1180-8. doi: 10.1172/JCI58649. Epub 2012 Apr 2. PMID:22466660 doi:10.1172/JCI58649
2. ↑ Voet, D., Voet, J.G., and C. Pratt. Fundamentals of Biochemistry 3rd Edition. Hoboken, NJ: John Wiley and Sons, 2008. Print.
3. ↑ Kudo M. Management of hepatocellular carcinoma: from prevention to molecular targeted therapy. Oncology. 2010 Jul;78 Suppl 1:1-6. Epub 2010 Jul 8. PMID:20616576 doi:10.1159/000315222
4. ↑ http://www.uniprot.org/uniprot/P00784
5. ↑ [1] Samuel, C.E. "Interferons, Interferon Receptors, Signal Transducer and Transcriptional Activators, and Inteferon Regulatory Factors." J Biol Chem 2007 282: 20045-20046. First Published on May 14, 2007, doi:10.1074/jbc.R700025200
6. ↑ Chill JH, Quadt SR, Levy R, Schreiber G, Anglister J. The human type I interferon receptor: NMR structure reveals the molecular basis of ligand binding. Structure. 2003 Jul;11(7):791-802. PMID:12842042

Relevant 3D Structures

Interferon Beta

1au1 - Homo sapiens

1ifa, 1wu3 - Mus musculus

Interferon Receptors

3s98, 3se3, 3se4, 1n6u, 1n6v, 2hym, 2kz1, 2lag, 3s8w, 3s9d - Homo sapiens