Assciation of Acetylcholinesterase and Butyrylcholinesterase Enzymes with Alzheimer's Disease

Year 2022, , 2386 - 2395, 01.12.2022

Zahide Demir , Fikret Türkan

https://doi.org/10.21597/jist.1161271

Cited By: 5

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease that is mostly seen in the elderly population, is clinically characterized by memory and cognitive disorders, and causes irreversible damage to neuron cells. Many reasons such as the unknown causes of the disease, the increase in the number of patients with the increase in life expectancy, the decrease in the quality of life of the disease, and the high cost of treatment have increased the importance of the disease and directed researchers to this field. Although the etiology of the disease is not clarified, some hypotheses try to explain the cause of the disease. These are the cholinergic hypothesis, the amyloid hypothesis, the tau hypothesis, and the oxidative stress hypothesis. The cholinergic hypothesis is the only hypothesis that explains the cause of Alzheimer's disease and is still accepted. According to the cholinergic hypothesis, the decrease in the amount of acetylcholine, an important neurotransmitter that increases learning and cholinergic activity in the nervous system, causes Alzheimer's disease. Acetylcholine is synthesized by the cholineacetyltransferase (ChAT) enzyme in the nervous system, and hydrolyzed by Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) enzymes. In this study, the association of AChE and BChE cholinesterase enzymes with Alzheimer's disease was evaluated.

Keywords

Alzheimer, acetylcholine, AChE, BChE, inhibitors

Asetilkolinesteraz ve Bütirilkolinesteraz Enzimlerinin Alzheimer Hastalığı ile İlişkisi

Abstract

Alzheimer hastalığı (AH) daha çok yaşlı popülasyonda görülen, klinik olarak hafıza ve bilişsel bozukluklar ile karakterize olan, geri dönüşümü olmayan nöron hücrelerinin hasarına yol açan bir nörodejeneratif hastalıktır. Hastalığının sebeplerinin tam olarak bilinmemesi, yaşama suresinin artmasıyla birlikte hasta sayısının gittikçe artması, hastalığın yaşam kalitesini çok fazla düşürmesi, tedavi maliyetinin çok yüksek olması gibi birçok neden hastalığın önemini artırmış ve araştırmacıların bu alana yönlendirmiştir. Hastalığın etiyolojisinin aydınlatılmamasına rağmen bazı hipotezlerle hastalığın nedeni açıklamaya çalışılmaktadır. Bunlar kolinerjik hipotez, amiloid hipotezi, tau hipotezi ve oksidatif stres hipotezidir. Kolinerjik hipotezi Alzheimer hastalığını nedenini açıklayan ve halen kabul gören tek hipotezdir. Kolinerjik hipoteze göre sinir sisteminde öğrenme ve kolinerjik aktiviteyi artıran önemli bir nörotransmiter olan asetilkolin miktarının azalması Alzheimer’e sebep olmaktadır. Asetilkolin sinir siteminde kolinasetiltransferaz (ChAT) enzimi tarafından sentezlenir, Asetilkolinesteraz (AChE) ve Bütirilkolinesteraz (BChE) enzimi tarafından hidroliz edilir. Bu çalışmada AChE ve BChE kolinesteraz enzimlerinin Alzheimer hastalığı ile ilişkisi değerlendirilmiştir.

Keywords

AChE, BChE, Alzheimer hastalığı, asetilkolin, inhibitörler

References

• Akasofu S, Kimura M, Kosasa T, Sawada K, Ogura H, 2008. Study of Neuroprotection of Donepezil a Therapy for Alzheimer's Disease. Chemico-Biological İnteractions, 175(1-3): 222-226.
• Alzheimer Derneği. 2019. 2019 Alzheimer Hastalığı Gerçekleri ve Rakamları. Alzheimer ve Demans, 15 (3): 321-387.
• Anstey K, J. von Sanden, C, Salim A, O'Kearney R, 2007. Smoking as a Risk Factor For Dementia and Cognitive Decline: a Meta-Analysis of Prospective Studies. American Journal of Epidemiology, 166(4): 367-378.
• Arce MP, Rodríguez-Franco MI, Gonzalez-Munoz, GC, Pérez C, López B, Villarroya M, Conde S, 2009. Neuroprotective and Cholinergic Properties of Multifunctional Glutamic Acid Derivatives For the Treatment of Alzheimer’s Disease. Journal of Medicinal Chemistry, 52(22): 7249-7257.
• Bartus R T, Dean III R L, Beer B, & Lippa A S, (1982). The Cholinergic Hypothesis of Geriatric Memory Dysfunction. Science, 217(4558): 408-414.
• Berman H A, Yguerabide J, Taylor P, 1980. Fluorescence Energy Transfer on Acetylcholinesterase: Spatial Relationship Between Beripheral Site and Active Center. Biochemistry, 19(10): 2226-2235.
• Blackard Jr WG, Sood GK, Crowe, DR, Fallon MB, 1998. Tacrine: a Cause of Fatal Hepatotoxicity? Journal of Clinical Gastroenterology, 26(1): 57-59.
• Bourne Y, Taylor P, Bougis P E, Marchot P, 1999. Crystal Structure of Mouse Acetylcholinesterase: a Peripheral Site-Occluding Loop in a Tetrameric Assembly. Journal of Biological Chemistry, 274(5): 2963-2970.
• Clarke R, Smith AD, Jobst K A, Refsum H, Sutton L, Ueland P M, 1998. Folate, Vitamin B1, and Serum Total Homocysteine Evels in Confirmed Alzheimer Disease. Archives of Neurology, 55(11): 1449-1455.
• Contestabile A, 2011. The History of the Oholinergic Hypothesis. Behavioural Brain Research, 221(2): 334-340.
• Cummings J L, 2000. Cholinesterase İnhibitors: a New Class of Psychotropic Compounds. American Journal of Psychiatry, 157(1): 4-15.
• Gaugler J, James B, Johnson T, Marin A, Weuve J, 2019. Alzheimer’s Disease Facts and Figures. Alzheimers Dement 2019, 15(3): 321-87.
• Hardy J, Bogdanovic N, Winblad B, Portelius E, Andreasen N, Cedazo‐Minguez A, Zetterberg H, 2014. Pathways to Alzheimer's Disease. Journal of İnternal Medicine, 275(3): 296-303.
• Holzgrabe U, Kapková P, Alptüzün V, Scheiber J Kugelmann E, 2007. Targeting Acetylcholinesterase to Treat Neurodegeneration. Expert Opinion on Therapeutic Targets, 11(2): 161-179.
• Irmak Ş, 2021. Yeni̇ Kumari̇n Türevlerinin SH-SY5Y Hücre Hattı Üzerinde Anti-Alzheimer Etkilerinin Araştırılması (Master's thesis, Pamukkale Üniversitesi Fen Bilimleri Enstitüsü).
• Imramovský A, Pejchal V, Štěpánková Š, Vorčáková K, Jampílek J, Vančo J, Trejtnar F, 2013. Synthesis and İn Vitro Evaluation of New Derivatives of 2-substituted-6-fluorobenzo [d] Thiazoles as Cholinesterase İnhibitors. Bioorganic & Medicinal Chemistry, 21(7): 1735-1748.
• Jeger R V, 2013. Mens sana in Corpore Sano Revisited. European Heart İournal, 34(33): 2580-2581.
• Kocançı FG, Aslım B, 2016. Asetilkolinesterazın Yapısı ve İşlevleri ve Bitkilerin Asetilkolinesteraz İnhibitör Aktivitesi. Manas Ziraat Veterinerlik ve Yaşam Bilimleri Dergisi, 6 (1): 19-35.
• Lilienfeld S, 2002. Galantamine—a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer's disease. CNS drug reviews, 8(2), 159-176.
• Ma J C, Dougherty D A, 1997. The cation π İnteraction. Chemical Reviews, 97(5): 1303-1324.
• Miller L M, Wang Q, Telivala T P, Smith R J, Lanzirotti A, Miklossy J, 2006. Synchrotron-Based İnfrared and X-ray İmaging Şhows Focalized Accumulation of Cu and Zn Co-Localized With β-Amyloid Deposits in Alzheimer’s Disease. Journal of Structural Biology, 155(1): 30-37.
• Misson J, Kendall M J, 1997. Therapeutic Advances: Donepezil For the Treatment of Alzheimer's Disease. Journal of Clinical Pharmacy and Therapeutics, 22(4): 251-255.
• Öztürk G B, Karan M A, 2009. Alzheimer Hastalığının Fizyopatolojisi. Klinik Gelişim, 22(3): 36-45.
• Pratico D, 2008. Oxidative Stress Hypothesis in Alzheimer’s Disease: a Reappraisal. Trends in Pharmacological Sciences, 29(12): 609-615.
• Reyes JF, Vargas R., Kumar D, Cullen EI, Perdomo CA, Pratt RD, 2004. Steady‐State Pharmacokinetics, Pharmacodynamics and Tolerability of Donepezil Hydrochloride in Hepatically İmpaired Patients. British Journal of Clinical Pharmacology, 58: 9-17.
• Rafii MS, Aisen PS, 2015. Advances in Alzheimer’s Disease Drug Development. BMC Medicine, 13(1), 1-7.
• Raji CA, Ho AJ, Parikshak NN, Becker JT, Lopez OL, Kuller H, Thompson P M, 2010. Brain Structure and Obesity. Human Brain Mapping, 31(3): 353-364.
• Sağlik BN, 2019. Alzheimer Hastalığı Tedavisinde Kullanılacak Yeni Bileşiklerin Tasarımı, Sentezi ve Biyolojik Aktivite Çalışmaları.
• Schelterns P, Feldman H, 2003. Treatment of Alzheimer's Disease; Current Status and New Perspectives. The Lancet Neurology, 2(9): 539-547.
• Singh M, Kaur M, Kukreja H, Chugh R, Silakari O, Singh D, 2013. Acetylcholinesterase İnhibitors as Alzheimer Therapy: From Nerve Toxins to Neuroprotection. European İournal of Medicinal Chemistry, 70: 165-188.
• Sugimoto H, Ogura H, Arai Y, Iimura Y, Yamanishi Y, 2002. Research and Development of Donepezil Hydrochloride, a New Type of Acetylcholinesterase İnhibitor. The Japanese Journal of Pharmacology, 89(1): 7-20
• Terry RD, 1963. The Fine Structure of Neurofibrillary Tangles in Alzheimer's Disease.
• Toiber D, Berson A, Greenberg D, Melamed-Book N, Diamant S, Soreq H, 2008. N-Acetylcholinesterase-İnduced Apoptosis in Alzheimer's Disease. Plos One, 3(9), e3108.
• Whitmer R A, Gustafson DR, Barrett-Connor E, Haan MN, Gunderson E P, Yaffe K, 2008. Central Obesity and İncreased Risk of Dementia More Than Three Decades Later. Neurology, 71(14): 1057-1064.
• Wimo A, Jönsson L, Bond J, Prince M, Winblad B, International AD, 2013. The Worldwide Economic İmpact of Dementia 2010. Alzheimer's & Dementia, 9(1): 1-11.
• Xie W, Stribley JA, Chatonnet A, Wilder PJ, Rizzino A, McComb RD, Lockridge O, 2000. Postnatal Developmental Delay and Supersensitivity to Organophosphate in Gene-Targeted Mice Lacking Acetylcholinesterase. Journal of Pharmacology and Experimental Therapeutics, 293(3): 896-902.
• Zhang HY, Tang XC, 2000. Huperzin B, a Novel Acetylcholinesterase İnhibitor, Attenuates Hydrogen Peroxide İnduced İnjury in PC12 Cells. Neuroscience Letters, 292(1): 41-44.