Multiple sclerosis: Difference between revisions
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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. | 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. | ||
<StructureSection load=' | <StructureSection load='1tcr' size='400' side='right' caption='Click on the green links to the left to observe the various proteins involved in MS immunopathology (PDB entry: [[1tcr]])' scene='Multiple_sclerosis/Xtracllulrtcell/1'> | ||
== Immunopathology== | == 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 <scene name='Multiple_sclerosis/Cd8tcell/1'>CD8+ T cells</scene> (two ectodomains shown, [[3qzw]]), as well as a smaller amount of <scene name='Multiple_sclerosis/Cd4tcell/1'>CD4+ T cells</scene> ([[3t0e]]), <scene name='Multiple_sclerosis/Monocyte/1'>monocytes</scene> ([[2ra4]]), and rare <scene name='Multiple_sclerosis/B_cell/1'>B cells</scene> ([[4e96]]) and <scene name='Multiple_sclerosis/Plasma_cell/1'>plasma cells</scene> ([[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.<ref name="MS Nylander & Hafler" /><ref>PMID:20477831</ref><ref>PMID:12849456</ref><ref>PMID:21446022</ref> Many antigens have been investigated to determine whether they are the cause of <scene name='Multiple_sclerosis/Xtracllulrtcell/1'>T cell</scene> autoreactivity (extracellular domain shown) in the hopes to determine a single culprit including: <scene name='Multiple_sclerosis/Mbp/1'>myelin basic protein</scene> (MBP, [[1bx2]]) with a peptide shown; <scene name='Multiple_sclerosis/Plp/1'>proteolipid protein</scene> (PLP, [[2xpg]]) with peptide shown; <scene name='Multiple_sclerosis/Mog/1'>oligodendrocyte glycoprotein</scene> (MOG, [[3csp]]); oligodendroglia-specific enzyme transaldolase, and heat shock protein <scene name='Multiple_sclerosis/Alphabcrystallin/1'>alphaB crystallin</scene> ([[2y1z]]).<ref name="MS Nylander & Hafler" /> | 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 <scene name='Multiple_sclerosis/Cd8tcell/1'>CD8+ T cells</scene> (two ectodomains shown, [[3qzw]]), as well as a smaller amount of <scene name='Multiple_sclerosis/Cd4tcell/1'>CD4+ T cells</scene> ([[3t0e]]), <scene name='Multiple_sclerosis/Monocyte/1'>monocytes</scene> ([[2ra4]]), and rare <scene name='Multiple_sclerosis/B_cell/1'>B cells</scene> ([[4e96]]) and <scene name='Multiple_sclerosis/Plasma_cell/1'>plasma cells</scene> ([[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.<ref name="MS Nylander & Hafler" /><ref>PMID:20477831</ref><ref>PMID:12849456</ref><ref>PMID:21446022</ref> Many antigens have been investigated to determine whether they are the cause of <scene name='Multiple_sclerosis/Xtracllulrtcell/1'>T cell</scene> autoreactivity (extracellular domain shown, [[1tcr]]) in the hopes to determine a single culprit including: <scene name='Multiple_sclerosis/Mbp/1'>myelin basic protein</scene> (MBP, [[1bx2]]) with a peptide shown; <scene name='Multiple_sclerosis/Plp/1'>proteolipid protein</scene> (PLP, [[2xpg]]) with peptide shown; <scene name='Multiple_sclerosis/Mog/1'>oligodendrocyte glycoprotein</scene> (MOG, [[3csp]]); oligodendroglia-specific enzyme transaldolase, and heat shock protein <scene name='Multiple_sclerosis/Alphabcrystallin/1'>alphaB crystallin</scene> ([[2y1z]]).<ref name="MS Nylander & Hafler" /> | ||
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 <scene name='Multiple_sclerosis/Lingo-1ectodomain/1'>lingo-1 ectodomain</scene> is a module implicated in central nervous system repair inhibition.<ref name='Lingo-1'>PMID:17005555</ref> | |||
__NOTOC__ | |||
</Structure Section> | |||
<StructureSection load='1ifa' size='500' side='right' caption='Click on the green links to the left to see key structural features of Interferon Beta (PDB entry [[1ifa]])' scene='Multiple_sclerosis/Interferon_beta/1'> | |||
==Interferon-β== | ==Interferon-β== | ||
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== Other Treatments== | == Other Treatments== | ||
===Copaxone=== | ===Copaxone=== | ||
Revision as of 00:03, 22 April 2012
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] 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.[2]
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.
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References
- ↑ 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
- ↑ Loma I, Heyman R. Multiple sclerosis: pathogenesis and treatment. Curr Neuropharmacol. 2011 Sep;9(3):409-16. PMID:22379455 doi:10.2174/157015911796557911
Relevant 3D Structures
Interferon Beta
3t0e - Homo sapiens
Interferon Receptors
2wq9, 1tcr, 1bx2, 2xpg, 3csp, 2y1z, 1ifa, 2lag, 3s8w, 3s9d - Homo sapiens
