Alzheimer Hastalığının Patogenezinde Sideritis L. (Dağçayı) Türlerinin Biyokimyasal ve Moleküler Etkileri

Ulaş Değirmenci

doi:10.35440/hutfd.1555225

Review

Alzheimer Hastalığının Patogenezinde Sideritis L. (Dağçayı) Türlerinin Biyokimyasal ve Moleküler Etkileri

Year 2025, Volume: 22 Issue: 1, 189 - 194, 26.03.2025

Ulaş Değirmenci

https://doi.org/10.35440/hutfd.1555225

Abstract

ÖZ
İlerleyici bir nörodejeneratif hastalık olan Alzheimer hastalığı, kolinerjik sistemdeki eksiklikler, nörofibriler yumak ve amiloid plaklar şeklinde beta amiloid birikimi ile karakterizedir. Alzheimer hastalığını tanımlamak için kullanılan beta amiloid beyin proteinlerinin aynı zamanda hastalığın patogenezinde de rol aldığına yönelik kanıtlar amiloid-β hipotezini ortaya çıkarmıştır. Bu hipotez, serebral beta amiloid birikiminin tau patolojisine, nöroinflamasyona, nöronal kayba ve bilişsel bozukluğa yol açtığını ileri sürmektedir. Kolinerjik sistem öğrenme ve hafıza süreçlerinin düzenlenmesinde önemli bir rol oynamaktadır. Kolinerjik hipoteze göre, Alzheimer hastalığında kolinerjik fonksiyonlardaki bozulma neokorteks ve hipokampüsü içeren beyin bölgelerinde kritik öneme sahiptir. Ayrıca asetilkolinesteraz ve bütilkolinesterazın senil plak oluşumunun erken evrelerinde beta amiloid agregasyonunda önemli bir rol oynadığı bilinmektedir. Gama aminobütirik asit merkezi sinir sisteminde görev yapan en önemli inhibitör nörotransmitterdir ve disfonksiyonu Alzheimer hastalığı ile ilişkilendirilmektedir. Lamiaceae familyasından olan Sideritis cinsine ait bitkiler ülkemizde çoğunlukla Marmara, Ege ve Akdeniz bölgelerinde yetişmektedir. Sideritis bitkileri çok eski çağlardan bu yana folklorik tıpta çoğunlukla aromatik bitki çayı şeklinde kullanılmaktadır. Uçucu yağlarının Akdeniz tıbbında akciğer dezenfektanları, diüretikler, mide ilaçları ve sinir gevşetici maddeler olarak kullanımı birçok etnofarmakolojik makalede rapor edilmiştir. Son yıllarda yapılan çalışmalarda Sideritis L. türlerinin nörodejeneratif hastalıklarda da koruyucu ve iyileştirici etkiye sahip olabileceğine işaret edildiğinden, Alzheimer hastalığındaki biyokimyasal ve moleküler etkilerinin derlenmesi amaçlanmıştır.

Keywords

Alzheimer Hastalığı, Sideritis, Asetilkolin esteraz, beta Amiloid

References

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2. Benussi A, Grassi M, Palluzzi F, Koch G, Di Lazzaro V, Nar-done R, et al. Classification Accuracy of Transcranial Mag-netic Stimulation for the Diagnosis of Neurodegenerative Dementias. Ann Neurol. 2020; 87(3):394-404.
3. Armstrong RA, Lantos PL, Cairns NJ. Overlap between neu-rodegenerative disorders. Neuropathology. 2005; 25:111-24.
4. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: re-port of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984; 34(7):939-44.
5. Mayeux R. Biomarkers: potential uses and limitati-ons. NeuroRx. 2004; 1(2):182-88.
6. Chrem MP, Surace E, Bérgamo Y, Calandri I, Vázquez S, Sevlever G, et al. Biomarkers for Alzheimer's disease. Whe-re we stand and where we are headed. Medicina (B Aires). 2019; 79(Spec 6/1):546-51.
7. Takeda S. Progression of Alzheimer's disease, tau propaga-tion, and its modifiable risk factors. Neurosci Res. 2019; 141:36-42.
8. Güvenc A, Houghton PJ, Duman H, Coskun M, Sahin P. Anti-oxidant activity studies on selected Sideritis species native to Turkey. Pharmaceutical Biology. 2005; 43:173-77.
9. Aslan I, Kilic T, Gören A, Topcu G. Toxicity of acetone extract of Sideritis trojana and 7-epicandicandiol, 7-epicandicandiol diacetate and 18-acetylsideroxolagainst stored pests Acanthoscelides obtectus (Say), Sitophilus gra-narius (L.) and Ephestia kuehniella (Zell). Industrial Crops and Products. 2006; 23:171–76.
10. Loğoğlu E, Arslan S, Oktemer A, Sakõyan I. Biological activi-ties of some natural compounds from Sideritis sipylea Bo-iss. Phytother Res. 2006; 20(4):294-97.
11. Yaneva I, Balabanski V. History of the uses of Pirin moun-tain tea (Sideritis scardica Griseb) in Bulgaria. Bulg J Public Health. 2013; 5:48–57.
12. Stanoeva JP, Stefova M, Stefkov G, Kulevanova S, Alipieva K, Bankova V, et al. Chemotaxonomic contribution to the Side-ritis species dilemma on the Balkans. Biochem Syst Ecol. 2015; 61:477–87.
13. González-Burgos E, Carretero ME, Gómez-Serranillos MP. Sideritis spp.: uses, chemical composition and pharmacolo-gical activities--a review. J Ethnopharmacol. 2011;135(2):209-25.
14. Giuliani C, Bini LM, Papa F, Cristalli G, Sagratini G, Vittori S, et al. Glandular trichomes and essential oil composition of endemic Sideritis italica (Mill.) Greuter et Burdet from central Italy. Chem Biodivers. 2011; 8(12):2179-94.
15. Pala-Paúl J, Perez-Alonso MJ, Velasco-Negueruela A, Bal-lesteros MT, Sanz J. Essential oil composition of Sideritis hirsuta L. From guadalajara province, Spain. Flavour Frag-rance J. 2006; 21:410–15.
16. Liu PP, Xie Y, Meng XY, Kang JS. History and progress of hypotheses and clinical trials for Alzheimer's disease. Sig-nal Transduct Target Ther. 2019; 4:29.
17. DeMattos RB, Bales KR, Cummins DJ, Dodart JC, Paul SM, Holtzman DM. Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A. 2001; 98(15):8850-55.
18. Morales R, Callegari K, Soto C. Prion-like features of misfol-ded Aβ and tau aggregates. Virus Res. 2015; 207:106-12.
19. Knörle R. Extracts of Sideritis scardica as triple monoamine reuptake inhibitors. J Neural Transm (Vienna). 2012; 119(12):1477-82.
20. Dimpfel W, Schombert L, Feistel B. Ex vivo characterization of the action of Sideritis extract using electrical activity in the rat hippocampus slice preparation. Pharmacol Pharm. 2016, 7:407–16.
21. Chalatsa I, Arvanitis DA, Mikropoulou EV, Giagini A, Papa-dopoulou-Daifoti Z, Aligiannis N, et al. Beneficial effects of Sideritis scardica and Cichorium spinosum against amyloi-dogenic pathway and tau misprocessing in Alzheimer's Di-sease neuronal cell culture models. J Alzheimers Dis. 2018; 64(3):787-800.
22. Ververis A, Ioannou K, Kyriakou S, Violaki N, Panayiotidis MI, Plioukas M, et al. Sideritis scardica extracts demonstrate neuroprotective activity against Aβ25-35 Toxicity. Plants (Ba-sel). 2023; 12(8):1716.
23. Heiner F, Feistel B, Wink M. Sideritis scardica extracts inhibit aggregation and toxicity of amyloid-β in Caenorhabditis elegans used as a model for Alzhei-mer's disease. PeerJ. 2018; 6:e4683.
24. Hofrichter J, Krohn M, Schumacher T, Lange C, Feistel B, Walbroel B, et al. Sideritis spp. extracts enhance memory and learning in Alzheimer's β-Amyloidosis mouse models and aged C57Bl/6 mice. J Alzheimers Dis. 2016; 53(3):967-80.
25. Gioran A, Paikopoulos Y, Panagiotidou E, Rizou AEI, Nasi GI, Dimaki VD, et al. Beneficial effects of Sideritis clandesti-na extracts and Sideridiol against amyloid β toxicity. Anti-oxidants (Basel). 2024; 13(3):261.
26. Lane RM, Kivipelto M, Greig NH. Acetylcholinesterase and its inhibition in Alzheimer disease. Clin Neuropharmacol. 2004; 27(3):141-49.
27. Macdonald IR, Rockwood K, Martin E, Darvesh S. Cholines-terase inhibition in Alzheimer's disease: is specificity the answer?. J Alzheimers Dis. 2014; 42(2):379-84.
28. Wilkinson DG, Francis PT, Schwam E, Payne-Parrish J. Cho-linesterase inhibitors used in the treatment of Alzheimer's disease: the relationship between pharmacological effects and clinical efficacy. Drugs Aging. 2004; 21(7):453-78.
29. Shanks M, Kivipelto M, Bullock R, Lane R. Cholinesterase inhibition: is there evidence for disease-modifying ef-fects?. Curr Med Res Opin. 2009; 25(10):2439-46.
30. Orhan G, Orhan I, Subutay-Oztekin N, Ak F, Sener B. Con-temporary anticholinesterase pharmaceuticals of natural origin and their synthetic analogues for the treatment of Alzheimer's disease. Recent Pat CNS Drug Discov. 2009; 4(1):43-51.
31. Orhan IE. Implications of some selected flavonoids towards Alzheimer's disease with the emphasis on cholinesterase inhibition and their bioproduction by metabolic enginee-ring. Curr Pharm Biotechnol. 2014; 15(4):352-61.
32. Saxena M, Dubey R. Target Enzyme in Alzheimer's Disease: Acetylcholinesterase Inhibitors. Curr Top Med Chem. 2019; 19(4):264-75.
33. Ladner CJ, Lee JM. Pharmacological drug treatment of Alzheimer disease: the cholinergic hypothesis revisited. J Neuropathol Exp Neurol. 1998; 57(8):719-31.
34. Sharma K. Cholinesterase inhibitors as Alzheimer's thera-peutics (Review). Mol Med Rep. 2019; 20(2):1479-87.
35. Colombres M, Sagal JP, Inestrosa NC. An overview of the current and novel drugs for Alzheimer's disease with parti-cular reference to anti-cholinesterase compounds. Curr Pharm Des. 2004; 10(25):3121-30.
36. Anand P, Singh B. A review on cholinesterase inhibitors for Alzheimer's disease. Arch Pharm Res. 2013; 36(4):375-99.
37. Lazarova MI, Tancheva LP, Tasheva KN, Denev PN, Uzunova DN, Stefanova MO, et al. Effects of Sideritis scardica extract on Scopolamine-induced learning and memory im-pairment in mice. J Alzheimers Dis. 2023; 92(4):1289-1302.
38. Deveci E, Tel-Çayan G, Usluer Ö, Emin Duru M. Chemical composition, antioxidant, anticholinesterase and anti-Tyrosinase activities of essential oils of two Sideritis Species from Turkey. Iran J Pharm Res. 2019; 18(2):903-13.
39. Zengin G, Sarikurkcu C, Aktumsek A, Ceylan R. Sideritis galatica Bornm.: a source of multifunctional agents for the management of oxidative damage, Alzheimer's and diabe-tes mellitus. Journal of functional foods. 2014; 11:538-47.
40. McKernan RM, Rosahl TW, Reynolds DS, Sur C, Wafford KA, Atack JR, et al. Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABA(A) receptor alpha1 subtype. Nat Neurosci. 2000; 3(6):587-92.
41. Brejc K, van Dijk WJ, Klaassen RV, Schuurmans M, van Der Oost J, Smit AB, et al. Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic re-ceptors. Nature. 200; 411(6835):269-76.
42. Kloda JH, Czajkowski C. Agonist-, antagonist-, and benzodi-azepine-induced structural changes in the alpha1 Met113-Leu132 region of the GABAA receptor. Mol Pharmacol. 2007; 71(2):483-93.
43. Sharma B, Torres MM, Rodriguez S, Gangwani L, Kumar S. MicroRNA-502-3p regulates GABAergic synapse function in hippocampal neurons. Neural Regen Res. 2024; 19(12):2698-2707.
44. Kessler A, Sahin-Nadeem H, Lummis SC, Weigel I, Pisc-hetsrieder M, Buettner A, Villmann C. GABA(A) receptor modulation by terpenoids from Sideritis extracts. Mol Nutr Food Res. 2014 ;58(4):851-62.
45. van Brederode J, Atak S, Kessler A, Pischetsrieder M, Vill-mann C, Alzheimer C. The terpenoids Myrtenol and Verbe-nol act on δ subunit-containing GABAA receptors and en-hance tonic inhibition in dentate gyrus granule cells. Neurosci Lett. 2016; 628:91-7.

Biochemical and Molecular Effects of Sideritis L. (Dağçayı) Species in the Pathogenesis of Alzheimer's Disease

Year 2025, Volume: 22 Issue: 1, 189 - 194, 26.03.2025

Ulaş Değirmenci

https://doi.org/10.35440/hutfd.1555225

Abstract

Alzheimer's disease, a progressive neurodegenerative disease, is characterized by deficiencies in the cholinergic system and beta amyloid deposition in the form of neurofibrillary tangles and amyloid plaques. Evidence that beta amyloid brain proteins used to define Alzheimer's disease also play a role in the pathogenesis of the disease has led to the amyloid-β hypothesis. This hypothesis proposes that cerebral beta amyloid deposition leads to tau pathology, neuroinflammation, neuro-nal loss, and cognitive impairment. The cholinergic system plays an important role in the regula-tion of learning and memory processes. According to the cholinergic hypothesis, the impairment of cholinergic functions in Alzheimer's disease is of critical importance in brain regions including the neocortex and hippocampus. It is also known that acetylcholinesterase and butylcholinesterase play an important role in beta amyloid aggregation in the early stages of senile plaque formation. Gamma aminobutyric acid is the most important inhibitory neurotransmitter in the central nervous system and its dysfunction is associated with Alzheimer's disease. Plants belonging to the Sideritis genus, which is from the Lamiaceae family, grow mostly in the Marmara, Aegean and Mediterra-nean regions of our country. Sideritis plants have been used in folkloric medicine since ancient times, mostly in the form of aromatic herbal tea. The use of essential oils in Mediterranean medi-cine as lung disinfectants, diuretics, stomachic drugs and neurorelaxants has been reported in many ethnopharmacological articles. Since recent studies have indicated that Sideritis L. species may have protective and healing effects in neurodegenerative diseases, it was aimed to compile their biochemical and molecular effects.

Keywords: Alzheimer’s Disease, Sideritis, Acetylcholine esterase, beta Amyloid

Keywords

Alzheimer’s Disease, Sideritis, Acetylcholine esterase, beta Amyloid

References

1. GBD 2016 Neurology Collaborators. Global, regional, and national burden of neurological disorders, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019; 18:459–80.
2. Benussi A, Grassi M, Palluzzi F, Koch G, Di Lazzaro V, Nar-done R, et al. Classification Accuracy of Transcranial Mag-netic Stimulation for the Diagnosis of Neurodegenerative Dementias. Ann Neurol. 2020; 87(3):394-404.
3. Armstrong RA, Lantos PL, Cairns NJ. Overlap between neu-rodegenerative disorders. Neuropathology. 2005; 25:111-24.
4. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: re-port of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984; 34(7):939-44.
5. Mayeux R. Biomarkers: potential uses and limitati-ons. NeuroRx. 2004; 1(2):182-88.
6. Chrem MP, Surace E, Bérgamo Y, Calandri I, Vázquez S, Sevlever G, et al. Biomarkers for Alzheimer's disease. Whe-re we stand and where we are headed. Medicina (B Aires). 2019; 79(Spec 6/1):546-51.
7. Takeda S. Progression of Alzheimer's disease, tau propaga-tion, and its modifiable risk factors. Neurosci Res. 2019; 141:36-42.
8. Güvenc A, Houghton PJ, Duman H, Coskun M, Sahin P. Anti-oxidant activity studies on selected Sideritis species native to Turkey. Pharmaceutical Biology. 2005; 43:173-77.
9. Aslan I, Kilic T, Gören A, Topcu G. Toxicity of acetone extract of Sideritis trojana and 7-epicandicandiol, 7-epicandicandiol diacetate and 18-acetylsideroxolagainst stored pests Acanthoscelides obtectus (Say), Sitophilus gra-narius (L.) and Ephestia kuehniella (Zell). Industrial Crops and Products. 2006; 23:171–76.
10. Loğoğlu E, Arslan S, Oktemer A, Sakõyan I. Biological activi-ties of some natural compounds from Sideritis sipylea Bo-iss. Phytother Res. 2006; 20(4):294-97.
11. Yaneva I, Balabanski V. History of the uses of Pirin moun-tain tea (Sideritis scardica Griseb) in Bulgaria. Bulg J Public Health. 2013; 5:48–57.
12. Stanoeva JP, Stefova M, Stefkov G, Kulevanova S, Alipieva K, Bankova V, et al. Chemotaxonomic contribution to the Side-ritis species dilemma on the Balkans. Biochem Syst Ecol. 2015; 61:477–87.
13. González-Burgos E, Carretero ME, Gómez-Serranillos MP. Sideritis spp.: uses, chemical composition and pharmacolo-gical activities--a review. J Ethnopharmacol. 2011;135(2):209-25.
14. Giuliani C, Bini LM, Papa F, Cristalli G, Sagratini G, Vittori S, et al. Glandular trichomes and essential oil composition of endemic Sideritis italica (Mill.) Greuter et Burdet from central Italy. Chem Biodivers. 2011; 8(12):2179-94.
15. Pala-Paúl J, Perez-Alonso MJ, Velasco-Negueruela A, Bal-lesteros MT, Sanz J. Essential oil composition of Sideritis hirsuta L. From guadalajara province, Spain. Flavour Frag-rance J. 2006; 21:410–15.
16. Liu PP, Xie Y, Meng XY, Kang JS. History and progress of hypotheses and clinical trials for Alzheimer's disease. Sig-nal Transduct Target Ther. 2019; 4:29.
17. DeMattos RB, Bales KR, Cummins DJ, Dodart JC, Paul SM, Holtzman DM. Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A. 2001; 98(15):8850-55.
18. Morales R, Callegari K, Soto C. Prion-like features of misfol-ded Aβ and tau aggregates. Virus Res. 2015; 207:106-12.
19. Knörle R. Extracts of Sideritis scardica as triple monoamine reuptake inhibitors. J Neural Transm (Vienna). 2012; 119(12):1477-82.
20. Dimpfel W, Schombert L, Feistel B. Ex vivo characterization of the action of Sideritis extract using electrical activity in the rat hippocampus slice preparation. Pharmacol Pharm. 2016, 7:407–16.
21. Chalatsa I, Arvanitis DA, Mikropoulou EV, Giagini A, Papa-dopoulou-Daifoti Z, Aligiannis N, et al. Beneficial effects of Sideritis scardica and Cichorium spinosum against amyloi-dogenic pathway and tau misprocessing in Alzheimer's Di-sease neuronal cell culture models. J Alzheimers Dis. 2018; 64(3):787-800.
22. Ververis A, Ioannou K, Kyriakou S, Violaki N, Panayiotidis MI, Plioukas M, et al. Sideritis scardica extracts demonstrate neuroprotective activity against Aβ25-35 Toxicity. Plants (Ba-sel). 2023; 12(8):1716.
23. Heiner F, Feistel B, Wink M. Sideritis scardica extracts inhibit aggregation and toxicity of amyloid-β in Caenorhabditis elegans used as a model for Alzhei-mer's disease. PeerJ. 2018; 6:e4683.
24. Hofrichter J, Krohn M, Schumacher T, Lange C, Feistel B, Walbroel B, et al. Sideritis spp. extracts enhance memory and learning in Alzheimer's β-Amyloidosis mouse models and aged C57Bl/6 mice. J Alzheimers Dis. 2016; 53(3):967-80.
25. Gioran A, Paikopoulos Y, Panagiotidou E, Rizou AEI, Nasi GI, Dimaki VD, et al. Beneficial effects of Sideritis clandesti-na extracts and Sideridiol against amyloid β toxicity. Anti-oxidants (Basel). 2024; 13(3):261.
26. Lane RM, Kivipelto M, Greig NH. Acetylcholinesterase and its inhibition in Alzheimer disease. Clin Neuropharmacol. 2004; 27(3):141-49.
27. Macdonald IR, Rockwood K, Martin E, Darvesh S. Cholines-terase inhibition in Alzheimer's disease: is specificity the answer?. J Alzheimers Dis. 2014; 42(2):379-84.
28. Wilkinson DG, Francis PT, Schwam E, Payne-Parrish J. Cho-linesterase inhibitors used in the treatment of Alzheimer's disease: the relationship between pharmacological effects and clinical efficacy. Drugs Aging. 2004; 21(7):453-78.
29. Shanks M, Kivipelto M, Bullock R, Lane R. Cholinesterase inhibition: is there evidence for disease-modifying ef-fects?. Curr Med Res Opin. 2009; 25(10):2439-46.
30. Orhan G, Orhan I, Subutay-Oztekin N, Ak F, Sener B. Con-temporary anticholinesterase pharmaceuticals of natural origin and their synthetic analogues for the treatment of Alzheimer's disease. Recent Pat CNS Drug Discov. 2009; 4(1):43-51.
31. Orhan IE. Implications of some selected flavonoids towards Alzheimer's disease with the emphasis on cholinesterase inhibition and their bioproduction by metabolic enginee-ring. Curr Pharm Biotechnol. 2014; 15(4):352-61.
32. Saxena M, Dubey R. Target Enzyme in Alzheimer's Disease: Acetylcholinesterase Inhibitors. Curr Top Med Chem. 2019; 19(4):264-75.
33. Ladner CJ, Lee JM. Pharmacological drug treatment of Alzheimer disease: the cholinergic hypothesis revisited. J Neuropathol Exp Neurol. 1998; 57(8):719-31.
34. Sharma K. Cholinesterase inhibitors as Alzheimer's thera-peutics (Review). Mol Med Rep. 2019; 20(2):1479-87.
35. Colombres M, Sagal JP, Inestrosa NC. An overview of the current and novel drugs for Alzheimer's disease with parti-cular reference to anti-cholinesterase compounds. Curr Pharm Des. 2004; 10(25):3121-30.
36. Anand P, Singh B. A review on cholinesterase inhibitors for Alzheimer's disease. Arch Pharm Res. 2013; 36(4):375-99.
37. Lazarova MI, Tancheva LP, Tasheva KN, Denev PN, Uzunova DN, Stefanova MO, et al. Effects of Sideritis scardica extract on Scopolamine-induced learning and memory im-pairment in mice. J Alzheimers Dis. 2023; 92(4):1289-1302.
38. Deveci E, Tel-Çayan G, Usluer Ö, Emin Duru M. Chemical composition, antioxidant, anticholinesterase and anti-Tyrosinase activities of essential oils of two Sideritis Species from Turkey. Iran J Pharm Res. 2019; 18(2):903-13.
39. Zengin G, Sarikurkcu C, Aktumsek A, Ceylan R. Sideritis galatica Bornm.: a source of multifunctional agents for the management of oxidative damage, Alzheimer's and diabe-tes mellitus. Journal of functional foods. 2014; 11:538-47.
40. McKernan RM, Rosahl TW, Reynolds DS, Sur C, Wafford KA, Atack JR, et al. Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABA(A) receptor alpha1 subtype. Nat Neurosci. 2000; 3(6):587-92.
41. Brejc K, van Dijk WJ, Klaassen RV, Schuurmans M, van Der Oost J, Smit AB, et al. Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic re-ceptors. Nature. 200; 411(6835):269-76.
42. Kloda JH, Czajkowski C. Agonist-, antagonist-, and benzodi-azepine-induced structural changes in the alpha1 Met113-Leu132 region of the GABAA receptor. Mol Pharmacol. 2007; 71(2):483-93.
43. Sharma B, Torres MM, Rodriguez S, Gangwani L, Kumar S. MicroRNA-502-3p regulates GABAergic synapse function in hippocampal neurons. Neural Regen Res. 2024; 19(12):2698-2707.
44. Kessler A, Sahin-Nadeem H, Lummis SC, Weigel I, Pisc-hetsrieder M, Buettner A, Villmann C. GABA(A) receptor modulation by terpenoids from Sideritis extracts. Mol Nutr Food Res. 2014 ;58(4):851-62.
45. van Brederode J, Atak S, Kessler A, Pischetsrieder M, Vill-mann C, Alzheimer C. The terpenoids Myrtenol and Verbe-nol act on δ subunit-containing GABAA receptors and en-hance tonic inhibition in dentate gyrus granule cells. Neurosci Lett. 2016; 628:91-7.

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Details

Primary Language	Turkish
Subjects	Neurology and Neuromuscular Diseases
Journal Section	Review
Authors	Ulaş Değirmenci 0000-0001-5208-6430
Early Pub Date	March 24, 2025
Publication Date	March 26, 2025
Submission Date	September 24, 2024
Acceptance Date	January 16, 2025
Published in Issue	Year 2025 Volume: 22 Issue: 1

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Vancouver	Değirmenci U. Alzheimer Hastalığının Patogenezinde Sideritis L. (Dağçayı) Türlerinin Biyokimyasal ve Moleküler Etkileri. Harran Üniversitesi Tıp Fakültesi Dergisi. 2025;22(1):189-94.

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Harran Üniversitesi Tıp Fakültesi Dergisi _/Journal of Harran University Medical Faculty