Материалы доступны только для специалистов сферы здравоохранения. Авторизуйтесь или зарегистрируйтесь.
Влияние нитрендипина на Ca2+-гомеостаз нейронов и активность цитотоксических факторов при болезни Альцгеймера
Асташкин Е.И. Влияние нитрендипина на Ca2+-гомеостаз нейронов и активность цитотоксических факторов при болезни Альцгеймера. Consilium Medicum. 2017; 19 (10): 137–142. DOI: 10.26442/2075-1753_19.10.137-142
________________________________________________
Astashkin E.I. Effect of nitrendipine on Ca2+-homeostasis of neurons and activity of cytotoxic factors in Alzheimer's disease. Consilium Medicum. 2017; 19 (10): 137–142. DOI: 10.26442/2075-1753_19.10.137-142
Материалы доступны только для специалистов сферы здравоохранения. Авторизуйтесь или зарегистрируйтесь.
Аннотация
В обзоре рассматриваются гипотеза «амилоидного каскада» и «кальциевая» гипотеза в возникновении и прогрессировании болезни Альцгеймера в свете последних экспериментальных данных. Особое внимание уделено изменению гомеостаза ионов Са2+- и Са2+-сигнализации при действии на нейроны цитотоксических β-амилоидных пептидов (Аβ-пептидов) и гиперфосфорилированных тау-белков. На примере дигидропиридинового блокатора Са2+-каналов нитрендипина приводятся новые механизмы его защитного действия, связанные со снижением образования Аβ-пептидов и их удаления из мозга в кровь (клиренсом Аβ).
Ключевые слова: болезнь Альцгеймера, амилоидный каскад, кальциевая гипотеза, нитрендипин, блокаторы кальциевых каналов, β-амилоидные пептиды.
Ключевые слова: болезнь Альцгеймера, амилоидный каскад, кальциевая гипотеза, нитрендипин, блокаторы кальциевых каналов, β-амилоидные пептиды.
________________________________________________
The review considers the hypothesis of the "amyloid cascade" and the "calcium" hypothesis in the onset and progression of Alzheimer's disease in the light of recent experimental data. Particular attention is paid to the change in the homeostasis of Ca2+ and Ca2+ ions upon the action of cytotoxic β-amyloid peptides (Aβ-peptides) and hyperphosphorylated tau proteins on neurons. Using the example of the dihydropyridine blocker of Ca2+ -channels of nitrendipine, new mechanisms of its protective action are presented, which are associated with a decrease in the formation of Aβ-peptides and their removal from the brain into the blood (clearance Aβ).
Key words: Alzheimer's disease, amyloid cascade, calcium hypothesis, nitrendipine, calcium channel blockers, β-amyloid peptides.
Полный текст
Список литературы
1. Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT. Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med 2011; 1: a006189.
2. Magi S, Castaldo P, Macri ML et al. Intracellular calcium disregulation: implications for Alzheimer’s Disease. Hindawi Publishing Corporation. BioMed Res Int Volume 2016; Article ID 6701324.
3. Forette F et al. Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet 1998; 352: 1347–51.
4. Fritze J, Walden J et al. Clinical findings with nimodipine in dementia: test of the calcium hypothesis. J Neural Transm Suppl 1995; 46: 439–53.
5. Tollefson GD. Short-term effects of the calcium channel blocker nimodipine (Bay-e-9736) in the management of primary degenerative dementia. Biol Psychiatry 1990; 27: 1133–42.
6. Anekonda ThS, Quinn JF, Harris Ch et al. L-type voltage-gated calcium channel blockade with isradipine as a therapeutic strategy for Alzheimer’s disease. Neurobiol Dis 2011; 41 (1): 62–70.
7. Woltjer RL. Role of glutathione in intracellular amyloid-alpha precursor protein/carboxy-terminal fragment aggregation and associated cytotoxicity. J Neurochem 2005; 93: 1047–56.
8. Woltjer RL et al. Effects of chemical chaperones on oxidative stress and detergent-insoluble species formation following conditional expression of amyloid precursor protein carboxy-terminal fragment. Neurobiol Dis 2007; 25: 427–37.
9. Wadsworth TL et al. Evaluation of coenzyme Q as an antioxidant strategy for Alzheimer's disease. J Alzheimers Dis 2008; 14: 225–34.
10. Demuro A, Parker I, Stutzmann G.E. Calcium signaling and amyloid toxicity in Alzheimer disease. J Biol Chem 2010; 285 (17): 12463–8.
11. Berridge MJ. Calcium hypothesis of Alzheimer’s disease. Pflugers Arch – Eur J Physiol. DOI: 10.1007/s00424-009-0736-1
12. Kawahara M, Negishi-Kato M, Sadakane Y. Calcium dyshomeostasis and neurotoxicity of Alzheimer's beta-amyloid protein. Expert Rev Neurother 2009; 9 (5): 681–93.
13. Zhang Y, Li P, Feng J, Wu M. Dysfunction of NMDA receptors in Alzheimer’s disease. Neurol Sci 2016; 37: 1039–47.
14. Toda T, Noda Y, Ito G et al. Presenilin-2 mutation causes early amyloid accumulation and memory impairment in a transgenic mouse model of Alzheimer’s disease. Hindawi Publishing Corporation J Biomed Biotechnol Volume 2011; Article ID 617974.
15. Tu H, Nelson O, Bezprozvanny A et al. Presenilins Form ER Ca2+ Leak Channels, a Function Disrupted by Familial Alzheimer's Disease-Linked Mutations. Alzheimers Dis 2009; 16 (2): 211–24.
16. Xu X. g-Secretase Catalyzes Sequential Cleavages of the AbPP Transmembrane Domain. J Cell 2006; 126 (5): 981–93.
17. Supnet Ch, Bezprozvanny I. The dysregulation of intracellular calcium in Alzheimer disease. Cell Calcium 2010; 47 (2): 183–9.
18. Nussbaum JM, Seward ME, Bloom GS. Alzheimer disease. A tale of two prions. Prion 2013; 7 (1): 14–9.
19. Shu-Ming Huang, Akihiro Mouri, Hideko Kokubo et al. Neprilysin-sensitive synapse-associated amyloid-b peptide oligomers impair neuronal plasticity and cognitive function. J Biol Chem 2006; 281 (26): 17941–51.
20. Eisele Y, Monteiro C, Fearns C et al. Targeting Protein Aggregation for the Treatment of Degenerative Diseases. Nat Rev Drug Discov 2015; 14 (11): 759–80.
21. Forette F et al. The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study. Arch Intern Med 2002; 162: 2046–52.
22. Hanon O, Forette F. Prevention of dementia: lessons from SYST-EUR and PROGRESS. J Neurol Sci 2004; 226: 71–4.
23. Paris D, Bachmeier C, Patel N. Selective antihypertensive dihydropyridines lower Ab accumulation by targeting both the production and the clearance of Ab across the Blood-Brain Barrier. Mol Med 2011; 17 (3–4): 149–62.
24. Bachmeier C, Beaulieu-Abdelahad D, Mullan M, Paris D. Selective dihydropyiridine compounds facilitate the clearance of beta-amyloid across the blood-brain barrier. Eur J Pharmacol 2011; 659: 124–9.
25. Anekonda TS, Quinn JF. Calcium channel blocking as a therapeutic strategy for Alzheimer's disease. The case for isradipine. Biochim Biophys Acta 2011; 1812: 1584–90.
26. Lopez-Arrieta JM, Birks J. Nimodipine for primary degenerative, mixed and vascular dementia. Cochrane Database Syst Rev 2002. CD000147.
27. Facchinetti F, Fasolato C, Del Giudice E et al. Nimodipine selectively stimulates beta-amyloid 1–42 secretion by a mechanism independent of calcium influx blockage. Neurobiol Aging 2006; 27: 218–27.
28. Zhang L, Yu J, Pan H et al. Small molecule regulators of autophagy identified by an image-based high-throughput screen. Proc Natl Acad Sci USA 2007; 104: 19023–8.
29. Mai A, Valente S, Meade S et al. Study of 1,4-dihydropyridine structural scaffold: discovery of novel sirtuin activators and inhibitors. J Med Chem 2009; 52: 5496–504.
30. Deane R, Yan ShD, Submamaryan RK et al. RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. Nat Med 2003; 9: 907–13.
31. Shibata M al. Clearance of Alzheimer’s amyloid-ss(1–40) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier. J Clin Invest 2000; 106: 1489–99.
32. Gosselet F, Saint-Pol J, Candela P, Fenart L. Amyloid-peptides, Alzheimer's Disease and the Blood-Brain Barrier. Cur Alzheimer Res 2013; 10: 1–19.
33. Bachmeier C, Mullan M, Paris D. Characterization and use of human brain microvascular endothelial cells to examine beta-amyloid exchange in the blood-brain barrier. Cytotechnology 2010; 62: 519–29.
34. Bell RD, Zlokovic BV. Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer’s disease. Acta Neuropathol 2009; 118: 103–13.
35. Deane R, Bell RD, Sagare A, Zlokovic BV. Clearance of amyloid-beta peptide across the blood-brain barrier: implication for therapies in Alzheimer’s disease. CNS Neurol Disord Drug Targets 2009; 8: 16–30.
36. Zlokovic BV, Yamada S, Holtzman D et al. Clearance of amyloid beta-peptide from brain: transport or metabolism? Nat Med 2000; 6: 718–9.
2. Magi S, Castaldo P, Macri ML et al. Intracellular calcium disregulation: implications for Alzheimer’s Disease. Hindawi Publishing Corporation. BioMed Res Int Volume 2016; Article ID 6701324.
3. Forette F et al. Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet 1998; 352: 1347–51.
4. Fritze J, Walden J et al. Clinical findings with nimodipine in dementia: test of the calcium hypothesis. J Neural Transm Suppl 1995; 46: 439–53.
5. Tollefson GD. Short-term effects of the calcium channel blocker nimodipine (Bay-e-9736) in the management of primary degenerative dementia. Biol Psychiatry 1990; 27: 1133–42.
6. Anekonda ThS, Quinn JF, Harris Ch et al. L-type voltage-gated calcium channel blockade with isradipine as a therapeutic strategy for Alzheimer’s disease. Neurobiol Dis 2011; 41 (1): 62–70.
7. Woltjer RL. Role of glutathione in intracellular amyloid-alpha precursor protein/carboxy-terminal fragment aggregation and associated cytotoxicity. J Neurochem 2005; 93: 1047–56.
8. Woltjer RL et al. Effects of chemical chaperones on oxidative stress and detergent-insoluble species formation following conditional expression of amyloid precursor protein carboxy-terminal fragment. Neurobiol Dis 2007; 25: 427–37.
9. Wadsworth TL et al. Evaluation of coenzyme Q as an antioxidant strategy for Alzheimer's disease. J Alzheimers Dis 2008; 14: 225–34.
10. Demuro A, Parker I, Stutzmann G.E. Calcium signaling and amyloid toxicity in Alzheimer disease. J Biol Chem 2010; 285 (17): 12463–8.
11. Berridge MJ. Calcium hypothesis of Alzheimer’s disease. Pflugers Arch – Eur J Physiol. DOI: 10.1007/s00424-009-0736-1
12. Kawahara M, Negishi-Kato M, Sadakane Y. Calcium dyshomeostasis and neurotoxicity of Alzheimer's beta-amyloid protein. Expert Rev Neurother 2009; 9 (5): 681–93.
13. Zhang Y, Li P, Feng J, Wu M. Dysfunction of NMDA receptors in Alzheimer’s disease. Neurol Sci 2016; 37: 1039–47.
14. Toda T, Noda Y, Ito G et al. Presenilin-2 mutation causes early amyloid accumulation and memory impairment in a transgenic mouse model of Alzheimer’s disease. Hindawi Publishing Corporation J Biomed Biotechnol Volume 2011; Article ID 617974.
15. Tu H, Nelson O, Bezprozvanny A et al. Presenilins Form ER Ca2+ Leak Channels, a Function Disrupted by Familial Alzheimer's Disease-Linked Mutations. Alzheimers Dis 2009; 16 (2): 211–24.
16. Xu X. g-Secretase Catalyzes Sequential Cleavages of the AbPP Transmembrane Domain. J Cell 2006; 126 (5): 981–93.
17. Supnet Ch, Bezprozvanny I. The dysregulation of intracellular calcium in Alzheimer disease. Cell Calcium 2010; 47 (2): 183–9.
18. Nussbaum JM, Seward ME, Bloom GS. Alzheimer disease. A tale of two prions. Prion 2013; 7 (1): 14–9.
19. Shu-Ming Huang, Akihiro Mouri, Hideko Kokubo et al. Neprilysin-sensitive synapse-associated amyloid-b peptide oligomers impair neuronal plasticity and cognitive function. J Biol Chem 2006; 281 (26): 17941–51.
20. Eisele Y, Monteiro C, Fearns C et al. Targeting Protein Aggregation for the Treatment of Degenerative Diseases. Nat Rev Drug Discov 2015; 14 (11): 759–80.
21. Forette F et al. The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study. Arch Intern Med 2002; 162: 2046–52.
22. Hanon O, Forette F. Prevention of dementia: lessons from SYST-EUR and PROGRESS. J Neurol Sci 2004; 226: 71–4.
23. Paris D, Bachmeier C, Patel N. Selective antihypertensive dihydropyridines lower Ab accumulation by targeting both the production and the clearance of Ab across the Blood-Brain Barrier. Mol Med 2011; 17 (3–4): 149–62.
24. Bachmeier C, Beaulieu-Abdelahad D, Mullan M, Paris D. Selective dihydropyiridine compounds facilitate the clearance of beta-amyloid across the blood-brain barrier. Eur J Pharmacol 2011; 659: 124–9.
25. Anekonda TS, Quinn JF. Calcium channel blocking as a therapeutic strategy for Alzheimer's disease. The case for isradipine. Biochim Biophys Acta 2011; 1812: 1584–90.
26. Lopez-Arrieta JM, Birks J. Nimodipine for primary degenerative, mixed and vascular dementia. Cochrane Database Syst Rev 2002. CD000147.
27. Facchinetti F, Fasolato C, Del Giudice E et al. Nimodipine selectively stimulates beta-amyloid 1–42 secretion by a mechanism independent of calcium influx blockage. Neurobiol Aging 2006; 27: 218–27.
28. Zhang L, Yu J, Pan H et al. Small molecule regulators of autophagy identified by an image-based high-throughput screen. Proc Natl Acad Sci USA 2007; 104: 19023–8.
29. Mai A, Valente S, Meade S et al. Study of 1,4-dihydropyridine structural scaffold: discovery of novel sirtuin activators and inhibitors. J Med Chem 2009; 52: 5496–504.
30. Deane R, Yan ShD, Submamaryan RK et al. RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. Nat Med 2003; 9: 907–13.
31. Shibata M al. Clearance of Alzheimer’s amyloid-ss(1–40) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier. J Clin Invest 2000; 106: 1489–99.
32. Gosselet F, Saint-Pol J, Candela P, Fenart L. Amyloid-peptides, Alzheimer's Disease and the Blood-Brain Barrier. Cur Alzheimer Res 2013; 10: 1–19.
33. Bachmeier C, Mullan M, Paris D. Characterization and use of human brain microvascular endothelial cells to examine beta-amyloid exchange in the blood-brain barrier. Cytotechnology 2010; 62: 519–29.
34. Bell RD, Zlokovic BV. Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer’s disease. Acta Neuropathol 2009; 118: 103–13.
35. Deane R, Bell RD, Sagare A, Zlokovic BV. Clearance of amyloid-beta peptide across the blood-brain barrier: implication for therapies in Alzheimer’s disease. CNS Neurol Disord Drug Targets 2009; 8: 16–30.
36. Zlokovic BV, Yamada S, Holtzman D et al. Clearance of amyloid beta-peptide from brain: transport or metabolism? Nat Med 2000; 6: 718–9.
________________________________________________
1. Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT. Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med 2011; 1: a006189.
2. Magi S, Castaldo P, Macri ML et al. Intracellular calcium disregulation: implications for Alzheimer’s Disease. Hindawi Publishing Corporation. BioMed Res Int Volume 2016; Article ID 6701324.
3. Forette F et al. Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet 1998; 352: 1347–51.
4. Fritze J, Walden J et al. Clinical findings with nimodipine in dementia: test of the calcium hypothesis. J Neural Transm Suppl 1995; 46: 439–53.
5. Tollefson GD. Short-term effects of the calcium channel blocker nimodipine (Bay-e-9736) in the management of primary degenerative dementia. Biol Psychiatry 1990; 27: 1133–42.
6. Anekonda ThS, Quinn JF, Harris Ch et al. L-type voltage-gated calcium channel blockade with isradipine as a therapeutic strategy for Alzheimer’s disease. Neurobiol Dis 2011; 41 (1): 62–70.
7. Woltjer RL. Role of glutathione in intracellular amyloid-alpha precursor protein/carboxy-terminal fragment aggregation and associated cytotoxicity. J Neurochem 2005; 93: 1047–56.
8. Woltjer RL et al. Effects of chemical chaperones on oxidative stress and detergent-insoluble species formation following conditional expression of amyloid precursor protein carboxy-terminal fragment. Neurobiol Dis 2007; 25: 427–37.
9. Wadsworth TL et al. Evaluation of coenzyme Q as an antioxidant strategy for Alzheimer's disease. J Alzheimers Dis 2008; 14: 225–34.
10. Demuro A, Parker I, Stutzmann G.E. Calcium signaling and amyloid toxicity in Alzheimer disease. J Biol Chem 2010; 285 (17): 12463–8.
11. Berridge MJ. Calcium hypothesis of Alzheimer’s disease. Pflugers Arch – Eur J Physiol. DOI: 10.1007/s00424-009-0736-1
12. Kawahara M, Negishi-Kato M, Sadakane Y. Calcium dyshomeostasis and neurotoxicity of Alzheimer's beta-amyloid protein. Expert Rev Neurother 2009; 9 (5): 681–93.
13. Zhang Y, Li P, Feng J, Wu M. Dysfunction of NMDA receptors in Alzheimer’s disease. Neurol Sci 2016; 37: 1039–47.
14. Toda T, Noda Y, Ito G et al. Presenilin-2 mutation causes early amyloid accumulation and memory impairment in a transgenic mouse model of Alzheimer’s disease. Hindawi Publishing Corporation J Biomed Biotechnol Volume 2011; Article ID 617974.
15. Tu H, Nelson O, Bezprozvanny A et al. Presenilins Form ER Ca2+ Leak Channels, a Function Disrupted by Familial Alzheimer's Disease-Linked Mutations. Alzheimers Dis 2009; 16 (2): 211–24.
16. Xu X. g-Secretase Catalyzes Sequential Cleavages of the AbPP Transmembrane Domain. J Cell 2006; 126 (5): 981–93.
17. Supnet Ch, Bezprozvanny I. The dysregulation of intracellular calcium in Alzheimer disease. Cell Calcium 2010; 47 (2): 183–9.
18. Nussbaum JM, Seward ME, Bloom GS. Alzheimer disease. A tale of two prions. Prion 2013; 7 (1): 14–9.
19. Shu-Ming Huang, Akihiro Mouri, Hideko Kokubo et al. Neprilysin-sensitive synapse-associated amyloid-b peptide oligomers impair neuronal plasticity and cognitive function. J Biol Chem 2006; 281 (26): 17941–51.
20. Eisele Y, Monteiro C, Fearns C et al. Targeting Protein Aggregation for the Treatment of Degenerative Diseases. Nat Rev Drug Discov 2015; 14 (11): 759–80.
21. Forette F et al. The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study. Arch Intern Med 2002; 162: 2046–52.
22. Hanon O, Forette F. Prevention of dementia: lessons from SYST-EUR and PROGRESS. J Neurol Sci 2004; 226: 71–4.
23. Paris D, Bachmeier C, Patel N. Selective antihypertensive dihydropyridines lower Ab accumulation by targeting both the production and the clearance of Ab across the Blood-Brain Barrier. Mol Med 2011; 17 (3–4): 149–62.
24. Bachmeier C, Beaulieu-Abdelahad D, Mullan M, Paris D. Selective dihydropyiridine compounds facilitate the clearance of beta-amyloid across the blood-brain barrier. Eur J Pharmacol 2011; 659: 124–9.
25. Anekonda TS, Quinn JF. Calcium channel blocking as a therapeutic strategy for Alzheimer's disease. The case for isradipine. Biochim Biophys Acta 2011; 1812: 1584–90.
26. Lopez-Arrieta JM, Birks J. Nimodipine for primary degenerative, mixed and vascular dementia. Cochrane Database Syst Rev 2002. CD000147.
27. Facchinetti F, Fasolato C, Del Giudice E et al. Nimodipine selectively stimulates beta-amyloid 1–42 secretion by a mechanism independent of calcium influx blockage. Neurobiol Aging 2006; 27: 218–27.
28. Zhang L, Yu J, Pan H et al. Small molecule regulators of autophagy identified by an image-based high-throughput screen. Proc Natl Acad Sci USA 2007; 104: 19023–8.
29. Mai A, Valente S, Meade S et al. Study of 1,4-dihydropyridine structural scaffold: discovery of novel sirtuin activators and inhibitors. J Med Chem 2009; 52: 5496–504.
30. Deane R, Yan ShD, Submamaryan RK et al. RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. Nat Med 2003; 9: 907–13.
31. Shibata M al. Clearance of Alzheimer’s amyloid-ss(1–40) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier. J Clin Invest 2000; 106: 1489–99.
32. Gosselet F, Saint-Pol J, Candela P, Fenart L. Amyloid-peptides, Alzheimer's Disease and the Blood-Brain Barrier. Cur Alzheimer Res 2013; 10: 1–19.
33. Bachmeier C, Mullan M, Paris D. Characterization and use of human brain microvascular endothelial cells to examine beta-amyloid exchange in the blood-brain barrier. Cytotechnology 2010; 62: 519–29.
34. Bell RD, Zlokovic BV. Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer’s disease. Acta Neuropathol 2009; 118: 103–13.
35. Deane R, Bell RD, Sagare A, Zlokovic BV. Clearance of amyloid-beta peptide across the blood-brain barrier: implication for therapies in Alzheimer’s disease. CNS Neurol Disord Drug Targets 2009; 8: 16–30.
36. Zlokovic BV, Yamada S, Holtzman D et al. Clearance of amyloid beta-peptide from brain: transport or metabolism? Nat Med 2000; 6: 718–9.
Авторы
Е.И.Асташкин
ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М.Сеченова» Минздрава России. 119991, Россия, Москва, ул. Трубецкая, д. 8, стр. 1
ast-med@mail.ru
ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М.Сеченова» Минздрава России. 119991, Россия, Москва, ул. Трубецкая, д. 8, стр. 1
ast-med@mail.ru
________________________________________________
E.I.Astashkin
I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation. 119991, Russian Federation, Moscow, ul. Trubetskaia, d. 8, str. 1
ast-med@mail.ru
Цель портала OmniDoctor – предоставление профессиональной информации врачам, провизорам и фармацевтам.