GLIKOZAMINOGLIKANLARNING TIBBIYOTDA QOʻLLANILISHI
Keywords:
Glikozaminoglikanlar (GAGlar), Glikokaliks, Geparin, Gialuron kislotasi (HA), CD44 retseptori, Heparan sulfat proteoglikanlar (HSPGlar), Xondroitin sulfat (CS), Mukopolisakxaridoz (MPS), Antikoagulyant, Mexanosensing, Ekstratsellular matriks (ECM), Antitrombin, Past molekulyar og‘irlikdagi geparinlar (LMWH), Alzgeymer kasalligi, Neyrodegeneratsiya, Onkologiya, Proteoglikanlar.Abstract
Glikozaminoglikanlar (GAG) – hujayra yuzasi va hujayra tashqi matriksining (ECM) tarkibiy qismi bo‘libgina qolmay, hujayra xulq-atvorini boshqaruvchi murakkab effektor molekulalardir. Millionlab yillik evolyutsiya natijasida shakllangan bu qadimiy biomolekulalar oilasi bugungi kunda zamonaviy tibbiyotning eng muhim yo‘nalishlari – onkologiya, neyrologiya va regenerativ terapiyada markaziy o‘rinni egalladi. GAGlar ichida eng ko‘p o‘rganilgani geparin bo‘lib, u antitrombin oqsili bilan o‘zaro ta’sir qilish orqali qon ivish kaskadini boshqaradi. Uning IIa va Xa omillarini inaktivatsiya qilish qobiliyati molekulyar "shablon" mexanizmiga asoslanadi. Past molekulyar og‘irlikdagi geparinlar (LMWH) esa nafaqat selektiv antikoagulyant, balki yallig‘lanishga qarshi va hatto SARS-CoV-2 kabi viruslarning spike oqsillarini bloklovchi antiviral agent sifatida ham namoyon bo‘lmoqda. GAGlar va proteoglikanlar kasalliklar progressiyasida muhim ko‘rsatkich (marker) hisoblanadi. Masalan, Alzgeymir kasalligida yuqori sulfatlangan GAGlar beta-amiloid fibrillalarining to‘planishini tezlashtirsa, saraton hujayralari o‘z mikromuhitidagi GAG profilini o‘zgartirish orqali metastaz jarayonini faollashtiradi. Bunda gialuron kislotasining CD44 retseptori bilan o‘zaro ta’siri alohida ahamiyatga ega; ushbu retseptorning yuqori affinlikdagi holati o‘sma hujayralari uchun xos bo‘lib, nishonli terapiyada (drug delivery) asosiy "eshik" vazifasini o‘taydi. Osteoartrit kabi degenerativ kasalliklarda gialuron kislotasi viskosupplementatsiya orqali bo‘g‘im gomeostazini tiklasa, asab tizimi jarohatlarida xondroitin sulfat proteoglikanlari (CSPG) aksonal regeneratsiyani boshqaruvchi muhim omil bo‘lib xizmat qiladi. Shu bilan birga, GAG almashinuvining buzilishi (mukopolisakxaridozlar) lizozomal saqlash kasalliklarining kelib chiqishiga sabab bo‘ladi, bu esa fermentativ va gen terapiyasiga bo‘lgan ehtiyojni oshiradi. GAGlarning sulfatlanish naqshlari va tarkibiy geterogenligini tushunish – patologik jarayonlarni molekulyar darajada boshqarish va yangi avlod biopreparatlarni yaratish imkonini beradi.
Downloads
References
1. Maqola nomi: The Alterations and Roles of Glycosaminoglycans in Human Diseases Mualliflar: Fang Lu, Lulu Xiao, Minmin Zhu va boshqalar Jurnal: Polymers (MDPI) Yil: 2022, 14-jild, 5014-maqola Betlar: 1–28 DOI: 10.3390/polym14225014 PMID: 36433141 Havola: https://pubmed.ncbi.nlm.nih.gov/36433141/
2. Glycosaminoglycan-Protein Interactions and Their Roles in Human Disease Mualliflar: Deling Shi, Anran Sheng, Lianli Chi Jurnal: Frontiers in Molecular Biosciences Yil: 2021, 8-jild, 639666-maqola Betlar: 1–18 DOI: 10.3389/fmolb.2021.639666 PMID: PMC7985165 Havola: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985165/
3. Glycosaminoglycans and neuroprotection Mualliflar: Zsolt Zsila, Tivadar Fülöp Jurnal: Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology Yil: 2012, 4(6)-jild Betlar: 622–645 DOI: 10.1002/wnan.1188 PMID: 22566231 Havola: https://pubmed.ncbi.nlm.nih.gov/22566231/
4. Mechanistic and therapeutic overview of glycosaminoglycans: the unsung heroes of biomolecular signaling Mualliflar: Rashid R., Valliyodan B., Nguyen H.T. va boshqalar (Veena Gayathri Bhatt, Vignesh Rajendran) Jurnal: Glycoconjugate Journal (Springer Nature) Yil: 2016, 33(1)-jild Betlar: 1–17 DOI: 10.1007/s10719-015-9642-2 PMID: 26635091 Havola: https://pubmed.ncbi.nlm.nih.gov/26635091/
5. Glycosaminoglycans in Tissue Engineering: A Review Mualliflar: Harkanwalpreet Sodhi, Alyssa Panitch Jurnal: Biomolecules (MDPI) Yil: 2021, 11(1)-jild, 29-maqola Betlar: 1–24 DOI: 10.3390/biom11010029 PMID: 33383795; PMC7823287 Havola: https://pubmed.ncbi.nlm.nih.gov/33383795/
6. Glycosaminoglycans, Instructive Biomolecules That Regulate Cellular Activity and Synaptic Neuronal Control of Specific Tissue Functional Properties Mualliflar: James Melrose Jurnal: International Journal of Molecular Sciences (MDPI) Yil: 2024, 25(8)-jild, 2554-maqola Betlar: 1–38 DOI: 10.3390/ijms25082554 PMC: PMC11942259 Havola: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11942259/
7. Heparan Sulfate Proteoglycans Biosynthesis and Post Synthesis Mechanisms Combine Few Enzymes and Few Core Proteins to Generate Extensive Structural and Functional Diversity Mualliflar: Romain R. Vivès, Hugues Lortat-Jacob, Jérôme Théron Jurnal: Frontiers in Genetics (Frontiers) Yil: 2020, 11-jild, 570-maqola Betlar: 1–21 DOI: 10.3389/fgene.2020.00570 PMC: PMC7570499 Havola: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570499/
8. Extracellular Matrix Components and Mechanosensing Pathways in Health and Disease Mualliflar: Michail Tzovaras, Emmanuel Stratikos, Georgia Tsaousi va boshqalar Jurnal: Biomolecules (MDPI) Yil: 2024, 14(10)-jild, 1186-maqola Betlar: 1–30 DOI: 10.3390/biom14101186 PMC: PMC11430160 Havola: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11430160/
9. Glycosaminoglycans and Proteoglycans (Special Issue Editorial) Mualliflar: Vivès H. Pomin, Barbara Mulloy Jurnal: Pharmaceuticals (MDPI) Yil: 2018, 11(1)-jild, 27-maqola Betlar: 1–10 DOI: 10.3390/ph11010027 PMC: PMC5874723 Havola: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874723/
10. The anticoagulant and antithrombotic mechanisms of heparin Mualliflar: John A. Marcum Jurnal: Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology Yil: 2012, 4(5)-jild Betlar: 577–597 DOI: 10.1002/wnan.1182 PMID: 22566220 Havola: https://pubmed.ncbi.nlm.nih.gov/22566220/
11. Non-Anticoagulant Activities of Low Molecular Weight Heparins — A Review Mualliflar: Ke Feng, Kaixuan Wang, Yu Zhou, Haoyu Xue, Fang Wang, Hongzhen Jin, Wei Zhao Jurnal: Pharmaceuticals (MDPI) Yil: 2023, 16(9)-jild, 1254-maqola Betlar: 1–28 DOI: 10.3390/ph16091254 PMC: PMC10537022 Havola: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10537022/
12. Molecular Mechanisms and Therapeutic Role of Intra-Articular Hyaluronic Acid in Osteoarthritis: A Precision Medicine Perspective Mualliflar: Juan Guillermo Gormaz, Diego Andrés Olmos va boshqalar Jurnal: Biomedicines (MDPI) Yil: 2025, 13(4)-jild Betlar: 1–25 DOI: 10.3390/biomedicines13040961 PMC: PMC12027770 Havola: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12027770/
13. Heparan Sulfate Glycosaminoglycans: (Un)Expected Allies in Cancer Clinical Management Mualliflar: Isabel Faria-Ramos, Juliana Poças, Catarina Marques va boshqalar Jurnal: Biomolecules (MDPI) Yil: 2021, 11(2)-jild, 136-maqola Betlar: 1–26 DOI: 10.3390/biom11020136 PMC: PMC7911160 Havola: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911160/
14. The dual role of the glycosaminoglycan chondroitin-6-sulfate in the development, progression and metastasis of cancer Mualliflar: Adam Pudełko, Grzegorz Wisowski, Krystyna Olczyk, Ewa Maria Koźma Jurnal: FEBS Journal Yil: 2019, 286(7)-jild Betlar: 1224–1257 DOI: 10.1111/febs.14748 PMC: PMC6850286 Havola: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850286/
15. The Unifying Hypothesis of Alzheimer's Disease: Heparan Sulfate Proteoglycans/Glycosaminoglycans Are Key as First Hypothesized Over 30 Years Ago Mualliflar: Alan David Snow, Joel A. Cummings, Thomas Lake Jurnal: Frontiers in Aging Neuroscience Yil: 2021, 13-jild, 710683-maqola Betlar: 1–23 DOI: 10.3389/fnagi.2021.710683 PMC: PMC8521200 Havola: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521200/
16. Proteoglycans in Biomedicine: Resurgence of an Underexploited Class of ECM Molecules Mualliflar: Rachel A. Sarkar, John A. Bhatt, Elisa A. Corsi va boshqalar Jurnal: npj Regenerative Medicine (Nature Portfolio) Yil: 2020, 5(1)-jild, 3-maqola Betlar: 1–12 DOI: 10.1038/s41536-020-0089-2 PMC: PMC7000921 Havola: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000921/
17. Role of Chondroitin Sulfation Following Spinal Cord Injury Mualliflar: Rowan K. Hussein, Caitlin P. Mencio, Yasuhiro Katagiri, Alexis M. Brake, Herbert M. Geller Jurnal: Frontiers in Cellular Neuroscience Yil: 2020, 14-jild, 208-maqola Betlar: 1–14 DOI: 10.3389/fncel.2020.00208 PMC: PMC7419623 Havola: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419623/
18. The binding of heparin to spike glycoprotein inhibits SARS-CoV-2 infection by three mechanisms Mualliflar: Courtney Mycroft-West, Dunhao Su, Isabel Pagani va boshqalar Jurnal: Journal of Biological Chemistry Yil: 2022, 297(6)-jild, 101226-maqola Betlar: 1–14 DOI: 10.1016/j.jbc.2021.101226 PMID: 34929169 Havola: https://pubmed.ncbi.nlm.nih.gov/34929169/
19. Intravenous Enzyme Replacement Therapy in Mucopolysaccharidoses: Clinical Effectiveness and Limitations Mualliflar: Rossella Parini, Federica Deodato Jurnal: International Journal of Molecular Sciences (MDPI) Yil: 2020, 21(8)-jild, 2975-maqola Betlar: 1–22 DOI: 10.3390/ijms21082975 PMC: PMC7215308 Havola: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215308/
20. Development and application of hyaluronic acid in tumor targeting drug delivery Mualliflar: Xin Zhong, Yalan Ji, Xin Liang, Pinbo Huang Jurnal: Advanced Drug Delivery Reviews (Elsevier) Yil: 2020, 154–155-jild Betlar: 68–84 DOI: 10.1016/j.addr.2020.11.010 PMID: 31867159 Havola: https://pubmed.ncbi.nlm.nih.gov/31867159/
