Multiple sclerosis

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." Inflammation is the primary cause of damage in MS, and though 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 increase considerably, 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 remission in the neurological degradation. A constant autoimmune attack on the patient's body causes increasingly severe symptoms, which can sometimes lead to death.

Taking a biochemical look at the immunopathology and some of the various treatments that exist for MS helps in the understanding that MS is no longer a diagnosis which is hopeless, but is in fact full of hopeful and helpful treatments.

Immunopathology Classical MS pathology has been characterized by white matter plaques which are typically located in the subcortical or periventricular white matter, optic nerve sheaths, brain stem, and spinal cord. The lesions that occur in these regions are generally identified by perivascular infiltrates that contain clonally expanded (two ectodomains shown, 3qzw), as well as a smaller amount of (3t0e), (2ra4), and rare (4e96) and (2wq9). Pathologists disagree on whether there are different mechanisms for the inflammatory and degenerative components of MS, especially given that older patients have generally progressed further along with their degeneration. There are many proposed degeneration mechanisms including Wallerian degeneration secondary to demyelination, and axonal transection, damage from reactive oxygen species and nitric oxide, or energy failure from mitochondrial dysfunction. 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. 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. Interferons alpha and beta interact with a receptor at the surface of Interferon receptor 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.

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

Relevant 3D StructuresRelevant 3D Structures

Interferon BetaInterferon Beta

1au1 - Homo sapiens

1ifa, 1wu3 - Mus musculus

Interferon ReceptorsInterferon Receptors

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