Biology:Dystrophin-associated protein complex

From HandWiki

The dystrophin-associated protein complex, also known as the dystrophin-associated glycoprotein complex is a multiprotein complex that includes dystrophin and the dystrophin-associated proteins.[1] It is one of the two protein complexes that make up the costamere in striated muscle cells. The other complex is the integrin-vinculin-talin complex.

Structure

The dystrophin-associated protein complex includes dystrophin.[2][3] Dystrophin binds to actin of the cytoskeleton, and also to proteins in the extracellular matrix.[3]

The dystrophin-associated protein complex also contains dystrophin-associated proteins.[2] This includes a four subunit sarcoglycan complex, which is fixed to dystrophin in muscle cells.[4]

In the epithelia of the kidney, dystrophin may be replaced with utrophin.[3]

Aquaporin 4 may be connected to the dystrophin-associated protein complex.[5]

Function

The dystrophin-associated protein complex is important for cell structure and cell signalling.[3] It is one of two protein complexes found in the costamere in striated muscle fibres.

Clinical significance

Many forms of muscular dystrophy are associated with disorders of the dystrophin-associated protein complex.[6]

Muscular dystrophy, the result of mutations in the genes that encode for dystrophin and the associated proteins that binds to it can arise in various forms.[7] The most common form is known as Duchenne muscular dystrophy (DMD).[8] DMD is usually discovered in early childhood and is most often seen occurring in males. There are several associated symptoms that can be observed in such patients including but not limited to a delay in walking and sitting, difficulty in breathing and heart failure.[9][10] These symptoms are found as a result of the inability to synthesize dystrophin and associate protein complexes that leave muscles weak and unable to repair any damaged sustained. These perpetually weak muscles prohibit normal physical activity.[8]

Therapy

There has been extensive research to discover treatment for DMD. The most common drug treated against DMD is known to be Deflazacort yielding the greatest benefits with the most acceptable side effects. Physical therapy consists of varying exercises that aim to increase muscle strength and durability so to facilitate normal physical activity and is recommended to begin as early as possible after diagnosis. Contracture intervention is recommended for patients in the middle ambulatory stage. However, surgical approach to DMD is declining as less invasive treatment becomes available. While treatment for DMD has been observed to improve muscle function and quality of life, a cure to the debilitating disease remains to be found.[7][11]

Therapeutic Microdystrophin

References

  1. ↑ "The development of the myotendinous junction. A review". Muscles, Ligaments and Tendons Journal 2 (2): 53–63. April 2012. PMID 23738275. 
  2. ↑ 2.0 2.1 Dystrophin-Associated+Protein+Complex at the US National Library of Medicine Medical Subject Headings (MeSH)
  3. ↑ 3.0 3.1 3.2 3.3 "Scaffolding Proteins in Transport Regulation" (in en). CHAPTER 12 - Scaffolding Proteins in Transport Regulation. San Diego: Academic Press. 2008-01-01. pp. 325–341. doi:10.1016/b978-012088488-9.50015-2. ISBN 978-0-12-088488-9. 
  4. ↑ "Sarcoglycanopathies". Muscular Dystrophies. Handbook of Clinical Neurology. 101. Elsevier. 2011-01-01. pp. 41–46. doi:10.1016/b978-0-08-045031-5.00003-7. ISBN 9780080450315. 
  5. ↑ "Water Homeostasis Dysfunction in Epilepsy" (in en). Chapter 17 - Water Homeostasis Dysfunction in Epilepsy. San Diego: Academic Press. 2017-01-01. pp. 315–335. doi:10.1016/b978-0-12-803196-4.00017-5. ISBN 978-0-12-803196-4. 
  6. ↑ "The dystrophin-associated protein complex". Journal of Cell Science 115 (Pt 14): 2801–2803. July 2002. doi:10.1242/jcs.115.14.2801. PMID 12082140. http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=12082140. 
  7. ↑ 7.0 7.1 "The muscular dystrophies: from genes to therapies". Physical Therapy 85 (12): 1372–1388. December 2005. doi:10.1093/ptj/85.12.1372. PMID 16305275. 
  8. ↑ 8.0 8.1 "Improvement of survival in Duchenne Muscular Dystrophy: retrospective analysis of 835 patients". Acta Myologica 31 (2): 121–125. October 2012. PMID 23097603. 
  9. ↑ "The Dystrophin Complex: Structure, Function, and Implications for Therapy". Comprehensive Physiology 5 (3): 1223–1239. July 2015. doi:10.1002/cphy.c140048. ISBN 9780470650714. PMID 26140716. 
  10. ↑ "The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy: an evidence review". Orphanet Journal of Rare Diseases 12 (1): 79. April 2017. doi:10.1186/s13023-017-0631-3. PMID 28446219. 
  11. ↑ "Current treatment of adult Duchenne muscular dystrophy". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. The Muscular Dystrophies: Molecular Basis and Therapeutic Strategies 1772 (2): 229–237. February 2007. doi:10.1016/j.bbadis.2006.06.009. PMID 16887341. 
  12. ↑ "Dec 16,2021 | Chugai In-Licenses Gene Therapy Delandistrogene Moxeparvovec (SRP-9001) for Duchenne Muscular Dystrophy | News". https://www.chugai-pharm.co.jp/english/news/detail/20211216150001_885.html. 
  13. ↑ Mendell, Jerry R.; Sahenk, Zarife; Lehman, Kelly; Nease, Carrie; Lowes, Linda P.; Miller, Natalie F.; Iammarino, Megan A.; Alfano, Lindsay N. et al. (1 September 2020). "Assessment of Systemic Delivery of rAAVrh74.MHCK7.micro-dystrophin in Children With Duchenne Muscular Dystrophy: A Nonrandomized Controlled Trial" (in en). JAMA Neurology 77 (9): 1122–1131. doi:10.1001/jamaneurol.2020.1484. PMID 32539076. PMC 7296461. https://investorrelations.sarepta.com/static-files/ba326dff-2918-46bd-9a42-4ba73676a77f. Retrieved 9 November 2022. 
  14. ↑ "Delandistrogene moxeparvovec - Roche/Sarepta Therapeutics - AdisInsight". https://adisinsight.springer.com/drugs/800050822. 




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