Vikipediya

Lipofutsin

Lipofutsin - lizosomal hazm faoliyati natijasida hosil boʻlgan lipidlardan tashkil topuvchi sariq-jigarrang qoldiq pigment granula.[1][2] U jigar, buyrak, yurak mushagi, retinada, buyrak usti bezlari, nerv hujayralari va ganglion hujayralarida joylashgan qarish yoki “eskirish” pigmentlaridan biri hisoblanadi.[3]

Orqa miya harakat motoneyronlarida yigʻilgan lipofutsin granulalari (koʻk va sariq rangda)

Tuzilishi

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Lipofutsin toʻyinmagan yogʻ kislotalarining oksidlanish mahsuloti boʻlib, membrana shikastlanishi yoki mitoxondriya va lizosomalarning shikastlanishining natijasida yigʻilib boradi. Katta miqdordagi lipid tarkibidan tashqari, lipofutsin tarkibida shakar va metallar, jumladan simob, aluminiy, temir, mis va rux borligi maʼlum.[4] Lipofutsin oksidlangan oqsillardan (30-70%) va lipidlardan (20-50%) iborat modda sifatida ham qabul qilinadi.[5] Bu modda lipoxromning bir turi hisoblanadi[6] va yadro atrofida joylashadi. Lipofutsin toʻplanishini kalamushlarda proteaza ingibitori (leupeptin) yuborish orqali keltirib chiqarishi mumkin: bu modda yuborilgandan uch oy oʻtib lipofutsinga oʻxshash moddaning darajasi normal holatga qaytadi, bu muhim hisoblangan "lipofutsinning yoʻq qilinish" mexanizmi mavjudligini koʻrsatadi. Biroq, bu natija munozarali, chunki leupeptin qoʻzgʻatadigan material haqiqiy lipofusin ekanligi shubhali. "Haqiqiy lipofussin" in vitro parchalanishi mumkin emasligi haqida dalillar mavjud;[7][8][9] Toʻr pardani kuchli yorugʻlik bilan oqartirish zaharli kationik bis-pyridinium tuzi, N-retiniliden-N-retinil etanolamin (A2E) hosil boʻlishiga olib keladi, bu quruq va hoʻl makula degeneratsiyasiga olib keladi[10]. Ushbu kasallikda ham lipofutsinga oʻxshash moddalar toʻplanishi haqida dalillar mavjud.

Klinik ahamiyati

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Koʻzda lipofutsin toʻplanishi makula degeneratsiyasi, degenerativ kasallik[11] va makulaning irsiy Stargardt kasalligi kabilarga olib kelishi mumkin. Periferik nerv tizimida lipofutsinoz[1] deb nomlanuvchi lipofutsinning anormal toʻplanishi neyrodegenerativ kasalliklar oilasiga sababchi boʻlishi mumkin. Ulardan eng keng tarqalgani Batten kasalligidir. Bundan tashqari, lipofutsinning patologik toʻplanishi Altsgeymer kasalligi, Parkinson kasalligi, amiotrofik lateral skleroz, ba'zi lizosomal kasalliklar, akromegaliya, denervatsiya atrofiyasi, lipid miopatiyasi, oʻpkaning surunkali obstruktiv kasalligi[12] kabilarga sababchi boʻlishi mumkin. Shuningdek, miokarddagi lipofutsinning toʻplanishi inson yurak patologiyasiga sababchi boʻlishi, uning qarish xronologiyasini toʻgʻridan-toʻgʻri tushunishga yordam berishi mumkin[13].

Davolash

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Avvalo parhezga amal qilish bilan olib boriladi[4]. E vitamini va glutationning ko'payishi lipofutsin ishlab chiqarishni kamaytiradi yoki toʻxtatadi. Nootropik dori piratsetam kalamushlarning miya toʻqimalarida lipofutsinning toʻplanishini sezilarli darajada kamaytiradi[14].

Boshqa mumkin boʻlgan davolash usullari:

  • Centrophenoxine[15]
  • Acetyl-L-carnitine[16]
  • Ginkgo biloba[17]
  • Dimethylethanolamine
  • Curcumin[18]

Hoʻl makula degeneratsiyasini selektiv fototermoliz yordamida davolash mumkin, bunda impulsli fokuslanmagan lazer asosan lipofutsinga boy hujayralarni isitadi va oʻldiradi, bu esa sogʻlom hujayralarni koʻpaytirish va boʻshliqlarni toʻldirilishiga olib keladi. Soraprazan (remofuscin) hayvonlarda retinal pigment epiteliy hujayralaridan lipofutsinni olib tashlashi aniqlangan.[19]  Bu quruq yoshga bogʻliq makula degeneratsiyasi va Stargardt kasalligini davolash uchun yangi terapiya variantini ochdi. Endi bu dori "European Medicines Agency" tomonidan Stargardt kasalligini davolash uchun roʻyxatga kiritildi[20].

Manbalar

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  1. ↑ 1,0 1,1 Alberts, Daniel Albert (2012). Dorland's illustrated medical dictionary (32nd ed.). Philadelphia, PA: Saunders/Elsevier. p. 1062. ISBN 978-1-4160-6257-8.
  2. ↑ "Medical Definition of LIPOFUSCIN". www.merriam-webster.com.
  3. ↑ Young B, Lowe JS, Stevens A, Heath JW. Wheater's Functional Histology: A Text and Atlas. 6th ed. Elsevier
  4. ↑ 4,0 4,1 Chris Gaugler, "Lipofuscin Archived 2007-07-15 at the Wayback Machine", Stanislaus Journal of Biochemical Reviews May 1997
  5. ↑ Double, KL; Dedov, VN; Fedorow, H; Kettle, E; Halliday, GM; Garner, B; Brunk, UT (June 2008). "The comparative biology of neuromelanin and lipofuscin in the human brain". Cellular and Molecular Life Sciences. 65 (11): 1669–82. doi:10.1007/s00018-008-7581-9. PMID 18278576. S2CID 6833509.
  6. ↑ "lipochrome", The Free Dictionary, retrieved 2021-02-18
  7. ↑ Terman, A, Brunk, UT (1998). "On the degradability and exocytosis of ceroid/lipofuscin in cultured rat cardiac myocytes". Mech Ageing Dev. 100 (2): 145–156. doi:10.1016/S0047-6374(97)00129-2. PMID 9541135. S2CID 34448638.
  8. ↑ Elleder, M; Drahota, Z; Lisá, V; Mares, V; Mandys, V; Müller, J; Palmer, DN (1995). "Tissue culture loading test with storage granules from animal models of neuronal ceroid-lipofuscinosis (Batten disease): testing their lysosomal degradability by normal and Batten cells". Am J Med Genet. 57 (2): 213–221. doi:10.1002/ajmg.1320570220. PMID 7668332.
  9. ↑ Weng J, Mata NL, Azarian SM, Tzekov RT, Birch DG, Travis GH (July 1999). "Insights into the function of Rim protein in photoreceptors and etiology of Stargardt's disease from the phenotype in abcr knockout mice". Cell. 98 (1): 13–23. doi:10.1016/S0092-8674(00)80602-9. PMID 10412977. S2CID 18605680.
  10. ↑ Maeda A, Maeda T, Golczak M, Palczewski K (September 2008). "Retinopathy in mice induced by disrupted all-trans-retinal clearance". The Journal of Biological Chemistry. 283 (39): 26684–93. doi:10.1074/jbc.M804505200. PMC 2546559. PMID 18658157.
  11. ↑ John Lacey, "Harvard Medical signs agreement with Merck to develop potential therapy for macular degeneration", 23-May-2006
  12. ↑ Joakim Allaire; François Maltais; Pierre LeBlanc; Pierre-Michel Simard; François Whittom; Jean-François Doyon; Clermont Simard; Jean Jobin (2002). "Lipofuscin accumulation in the vastus lateralis muscle in patients with chronic obstructive pulmonary disease". Muscle and Nerve. 25 (3): 383–389. doi:10.1002/mus.10039. PMID 11870715. S2CID 22309073.
  13. ↑ Kakimoto, Yu; Okada, Chisa; Kawabe, Noboru; Sasaki, Ayumi; Tsukamoto, Hideo; Nagao, Ryoko; Osawa, Motoki (2019). "Myocardial lipofuscin accumulation in ageing and sudden cardiac death". Scientific Reports. 9 (1): 3304. Bibcode:2019NatSR...9.3304K. doi:10.1038/s41598-019-40250-0. ISSN 2045-2322. PMC 6397159. PMID 30824797.
  14. ↑ Paula-Barbosa, M.; et al. (1991). "The effects of Piracetam on lipofuscin of the rat cerebellar and hippocampa; neurons after long-term alcohol treatment and withdrawal". Alcoholism: Clinical and Experimental Research. 15 (5): 834–838. doi:10.1111/j.1530-0277.1991.tb00610.x. PMID 1755517.
  15. ↑ Roy, D; Pathak, DN; Singh, R (1983). "Effect of centrophenoxine on the antioxidative enzymes in various regions of the aging rat brain". Exp Gerontol. 18 (3): 185–97. doi:10.1016/0531-5565(83)90031-1. PMID 6416880. S2CID 29129359.
  16. ↑ Amenta F, Ferrante F, et al., Reduced lipofuscin accumulation in senescent rat brain by long-term acetyl-L-carnitine treatment. Arch Gerontol Geriatr. 1989 Sep-Oct;9(2):147-53.
  17. ↑ Huang, SZ; Luo, YJ; Wang, L; Cai, KY (Jan 2005). "Effect of ginkgo biloba extract on livers in aged rats". World J Gastroenterol. 11 (1): 132–5. doi:10.3748/wjg.v11.i1.132. PMC 4205372. PMID 15609412.
  18. ↑ Shen, Li-Rong; Parnell, Laurence D.; Ordovas, Jose M.; Lai, Chao-Qiang (January 2013). "Curcumin and aging". BioFactors. 39 (1): 133–140. doi:10.1002/biof.1086. ISSN 1872-8081. PMID 23325575. S2CID 39360837.
  19. ↑ Julien, S; Schraermeyer, U (Oct 2012). "Lipofuscin can be removed from the retinal pigment epithelium of monkeys". Neurobiol Aging. 33 (10): 2390–7. doi:10.1016/j.neurobiolaging.2011.12.009. PMID 22244091. S2CID 22829613.
  20. ↑ "EU/3/13/1208". Retrieved 1 June 2021. 
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