Preview

Neurology, Neuropsychiatry, Psychosomatics

Advanced search

Geroprotective properties of neuroprotective and neurotrophic peptides

https://doi.org/10.14412/2074-2711-2020-1-61-67

Full Text:

Abstract

Objective: to elucidate whether cerebrolysin contains peptide fragments that promote geroprotection.
Material and methods. The peptide composition of cerebrolysin underwent a comprehensive mass spectrometric analysis, followed by a systemic biological assessment.
Results and discussion. Thirty-six peptides with geroprotective properties were isolated in the multipeptide composition of cerebrolysin. These peptides included those of mimetics of adrenomedullin and enkephalins; those of inhibitors of seven targeted human proteins (the protein kinases MAPK1, VPRBP, and PKC, the gamma-secretase PS1, the kinases CDK1, SGK1 and mTOR). The established cerebrolysin peptides were shown to be competitive inhibitors of the seven targeted proteins. In particular, inhibition of PKC and mTOR stimulated the increased autophagy (the utilization of waste and abnormal proteins), which contributes to an increase in the survival of cells and model organisms.
Conclusion. Cerebrolysin can have geroprotective effects, by inhibiting the seven targeted proteins, by activating endorphinergic neurotransmission, and can be indirectly involved in vascular tone normalization.

About the Authors

O. A. Gromova
Federal Research Center «Informatics and Management», Russian Academy of Sciences; Big Data Storage and Analysis Center, M.V. Lomonosov Moscow State University
Russian Federation

44, Vavilov St., Build. 2, Moscow 119333

1, Leninskie Gory, Moscow 119234





I. Yu. Torshin
Federal Research Center «Informatics and Management», Russian Academy of Sciences; Big Data Storage and Analysis Center, M.V. Lomonosov Moscow State University
Russian Federation

44, Vavilov St., Build. 2, Moscow 119333

1, Leninskie Gory, Moscow 119234 



V. G. Zgoda
V.N. Orekhovich Research Institute of Biomedical Chemistry
Russian Federation
10, Pogodinskaya St., Build. 8, Moscow 119121



A. I. Sorokin
Big Data Storage and Analysis Center, M.V. Lomonosov Moscow State University
Russian Federation

1, Leninskie Gory, Moscow 119234 



O. V. Tikhonova
V.N. Orekhovich Research Institute of Biomedical Chemistry
Russian Federation
10, Pogodinskaya St., Build. 8, Moscow 119121



References

1. Ye J, Rawson RB, Komuro R, et al. ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol Cell. 2000 Dec;6(6):1355-64. doi: 10.1016/s1097-2765(00)00133-7.

2. Rokhlina ML, Kozlov AA, Usmanova NN, Smirnova EA. The use of Cerebrolysin in heroin addiction. Psikhiatriya i psikhofarmakoterapiya. 2001;(3):98-102. (In Russ.).

3. Zeeh J. Medication review – seven steps to improve pharmacotherapy in elderly adults. MMW Fortschr Med. 2016 Jun 9;158(11):54-7. doi: 10.1007/s15006-016-8383-x.

4. Gromova OA, Torshin IYu, Zgoda VG, Tikhonova OV. Complex proteomic analysis of the "light" peptide fraction of Cerebrolysin. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2019;119(8):75-83. (InRuss.).

5. He P, Lee SJ, Lin S, et al. Serum- and glucocorticoid-induced kinase 3 in recycling endosomes mediates acute activation of Na+/H+ exchanger NHE3 by glucocorticoids. Mol Biol Cell. 2011 Oct;22(20):3812-25. doi: 10.1091/mbc.E11-04-0328.

6. Glossmann HH, Lutz OMD. Metformin and Aging: A Review. Gerontology. 2019;65(6):581-590. doi: 10.1159/000502257. Epub 2019 Sep 13.

7. Torshin IYu, Gromova OA, Zgoda VG, et al. About the peptides of Cerebrolysin contributing mood stabilization. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2019;119(12): 68-74. (In Russ.).

8. Bornstein NM, Guekht A, Vester J, et al. Safety and efficacy of Cerebrolysin in early post-stroke recovery: a meta-analysis of nine randomized clinical trials. Neurol Sci. 2018 Apr;39(4):629-640. doi: 10.1007/s10072-017-3214-0.

9. Yoo D, Kim BY, Campo C, et al. Cell surface expression of the ROMK (Kir 1.1) channel is regulated by the aldosterone-induced kinase, SGK-1, and protein kinase A. J Biol Chem. 2003 Jun 20;278(25):23066-75. doi: 10.1074/jbc.M212301200.

10. Lee JM, Lee JS, Kim H, et al. EZH2 generates a methyl degron that is recognized by the DCAF1/DDB1/CUL4 E3 ubiquitin ligase complex. Mol Cell. 2012 Nov 30;48(4):572-86. doi: 10.1016/j.molcel.2012.09.004.

11. Zhang D, Dong Y, Li Y, et al. Efficacy and Safety of Cerebrolysin for Acute Ischemic Stroke: A Meta-Analysis of Randomized Controlled Trials. Biomed Res Int. 2017;2017: 4191670. doi: 10.1155/2017/4191670.

12. UniProt Consortium. UniProt: a worldwide hub of protein knowledge. Nucleic Acids Res. 2019 Jan 8;47(D1):D506-D515. doi: 10.1093/nar/gky1049.

13. Torshin IYu. Sensing the change from molecular genetics to personalized medicine. New York: Nova Biomedical Books.

14. Tamori Y, Bialucha CU, Tian AG, et al. Involvement of Lgl and Mahjong/VprBP in cell competition. PLoS Biol. 2010 Jul 13;8(7): e1000422. doi: 10.1371/journal.pbio.1000422.

15. Ghaffarpasand F, Torabi S, Rasti A, et al. Effects of cerebrolysin on functional outcome of patients with traumatic brain injury: a systematic review and meta-analysis. Neuropsychiatr Dis Treat. 2018 Dec 27;15:127-135. doi: 10.2147/NDT.S186865. eCollection 2019.

16. Torshin IY, Rudakov KV. On metric spaces arising during formalization of recognition and classification problems. Part 1: Properties of compactness. Pattern Recognition and Image Analysis. 2016;26(2):274-84.

17. Voskresenskaya ON, Zakharov NB, Tarasova YuS, et al. Possible mechanisms of cognitive dysfunction in patients with chronic forms of cerebrovascular diseases. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2018;10(1):32-36. (In Russ.). doi: 10.14412/2074-2711-2018-1-32-36

18. Gauthier S, ProaЦo JV, Jia J, et al. Cerebrolysin in mild-to-moderate Alzheimer's disease: a meta-analysis of randomized controlled clinical trials. Dement Geriatr Cogn Disord. 2015;39(5-6):332-47. doi: 10.1159/000377672.

19. Gromova OA, Torshin IYu, Fedotova LE. Geriatric information analysis of the molecular properties of mexidole. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2017;9(4):46–54. (In Russ.). doi: 10.14412/2074-2711-2017-4-46-54.

20. Torshin IYu, Rudakov KV. On metric spaces arising during formalization of problems of recognition and classification. Part 2: Density properties. Pattern Recognition and Image Analysis. 2016;26(3):483-96.

21. Gromova OA, Torshin IYu. Multimodal effect of Cerebrolysin against militant reductionism. Nevrologicheskii vestnik. 2008;(3):83-91. (In Russ.).

22. Torshin IYu, Gromova OA, Fedotova LE, Gromov AN. Comparative chemoreactome analysis of dexketoprofen, ketoprofen, and diclofenac. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2018;10(1):47-54. (In Russ.). doi: 10.14412/2074-2711-2018-1-47-54.

23. Torshin IYu, Rudakov KV. Combinatorial analysis of the solvability properties of the problems of recognition and completeness of algorithmic models. Part 2: metric approach within the framework of the theory of classification of feature values. Pattern Recognition and Image Analysis. 2017;27(2):184-99.

24. Chemer N, Bilanovskyi V. Cerebrolysin as a New Treatment Option for Post-Stroke Spasticity: Patient and Physician Perspectives. Neurol Ther. 2019 Jun;8(1):25-27. doi: 10.1007/s40120-019-0128-1.

25. Torshin IYu, Rudakov KV. On the theoretical basis of metric analysis of poorly formalized problems of recognition and classification. Pattern Recognition and Image Analysis. 2015; 25(4):577-87.

26. Rokhlina ML, Kozlov AA, Usmanova NN, Smirnova EA. The use of Cerebrolysin in heroin addiction. Psikhiatriya i psikhofarmakoterapiya. 2001;(3):98-102. (In Russ.).

27. Torshin IYu, Gromova OA, Lila AM, et al. Targeted action of glucosamine sulfate in combination of osteoarthritis and tumor pathology. Russkii meditsinskii zhurnal. 2019;(6):23-30. (In Russ.).

28. Gromova OA, Torshin IYu, Zgoda VG, Tikhonova OV. Complex proteomic analysis of the "light" peptide fraction of Cerebrolysin. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2019;119(8):75-83. (InRuss.).

29. Schmeisser K, Parker JA. Pleiotropic Effects of mTOR and Autophagy During Development and Aging. Front Cell Dev Biol. 2019 Sep 11;7:192. doi: 10.3389/fcell.2019.00192. eCollection 2019.

30. Torshin IYu, Gromova OA, Zgoda VG, et al. About the peptides of Cerebrolysin contributing mood stabilization. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2019;119(12): 68-74. (In Russ.).

31. Lim JS, Kim WI, Kang HC, et al. Brain somatic mutations in MTOR cause focal cortical dysplasia type II leading to intractable epilepsy. Nat Med. 2015 Apr;21(4):395-400. doi: 10.1038/nm.3824.

32. UniProt Consortium. UniProt: a worldwide hub of protein knowledge. Nucleic Acids Res. 2019 Jan 8;47(D1):D506-D515. doi: 10.1093/nar/gky1049.

33. Dephoure N, Zhou C, Villen J, et al. A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008;105(31):10762-7. doi: 10.1073/pnas.0805139105.

34. Torshin IYu. Sensing the change from molecular genetics to personalized medicine. New York: Nova Biomedical Books.

35. Koren I, Reem E, Kimchi A. DAP1, a novel substrate of mTOR, negatively regulates autophagy. Curr Biol. 2010;22;20(12):1093-8. doi: 10.1016/j.cub.2010.04.041.

36. Torshin IY, Rudakov KV. On metric spaces arising during formalization of recognition and classification problems. Part 1: Properties of compactness. Pattern Recognition and Image Analysis. 2016;26(2):274-84.

37. Blagosklonny MV. Rapamycin for longevity: opinion article. Aging (Albany NY). 2019 Oct 4; 11(19):8048-8067. doi: 10.18632/aging.102355. Epub 2019 Oct 4.

38. Torshin IYu, Rudakov KV. On metric spaces arising during formalization of problems of recognition and classification. Part 2: Density properties. Pattern Recognition and Image Analysis. 2016;26(3):483-96.

39. Numazaki M, Tominaga T, Toyooka H, Tominaga M. Direct phosphorylation of capsaicin receptor VR1 by protein kinase Cepsilon and identification of two target serine residues. J Biol Chem. 2002;277(16):13375-8. doi: 10.1074/jbc.C200104200.

40. Torshin IYu, Rudakov KV. Combinatorial analysis of the solvability properties of the problems of recognition and completeness of algorithmic models. Part 2: metric approach within the framework of the theory of classification of feature values. Pattern Recognition and Image Analysis. 2017;27(2):184-99.

41. Wang S, Ge W, Harns C, et al. Ablation of toll-like receptor 4 attenuates aging-induced myocardial remodeling and contractile dysfunction through NCoRI-HDAC1- mediated regulation of autophagy. J Mol Cell Cardiol. 2018 Jun; 119:40-50. doi: 10.1016/j.yjmcc.2018.04.009. Epub 2018 Apr 13.

42. Torshin IYu, Rudakov KV. On the theoretical basis of metric analysis of poorly formalized problems of recognition and classification. Pattern Recognition and Image Analysis. 2015; 25(4):577-87.

43. Ruan X, Arendshorst WJ. Role of protein kinase C in angiotensin II-induced renal vasoconstriction in genetically hypertensive rats. Am J Physiol. 1996 Jun;270(6 Pt 2):F945-52. doi: 10.1152/ajprenal.1996.270.6.F945.

44. Torshin IYu, Gromova OA, Lila AM, et al. Targeted action of glucosamine sulfate in combination of osteoarthritis and tumor pathology. Russkii meditsinskii zhurnal. 2019;(6):23-30. (In Russ.).

45. Uneda K, Wakui H, Maeda A, et al. Angiotensin II Type 1 Receptor-Associated Protein Regulates Kidney Aging and Lifespan Independent of Angiotensin. J Am Heart Assoc. 2017 Jul 27;6(8). pii: e006120. doi: 10.1161/JAHA.117.006120.

46. Schmeisser K, Parker JA. Pleiotropic Effects of mTOR and Autophagy During Development and Aging. Front Cell Dev Biol. 2019 Sep 11;7:192. doi: 10.3389/fcell.2019.00192. eCollection 2019.

47. Fluhrer R, Friedlein A, Haass C, Walter J. Phosphorylation of presenilin 1 at the caspase recognition site regulates its proteolytic processing and the progression of apoptosis. J Biol Chem. 2004 Jan 16;279(3):1585-93. Epub 2003 Oct 22.

48. Lim JS, Kim WI, Kang HC, et al. Brain somatic mutations in MTOR cause focal cortical dysplasia type II leading to intractable epilepsy. Nat Med. 2015 Apr;21(4):395-400. doi: 10.1038/nm.3824.

49. Torshin IYu, Gromova OA. Ekspertnyi analiz dannykh v molekulyarnoi farmakologii [Expert data analysis in molecular pharmacology]. Moscow: MTsNMO; 2012. 748 p

50. Dephoure N, Zhou C, Villen J, et al. A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008;105(31):10762-7. doi: 10.1073/pnas.0805139105.

51. Sadin AV, Zhidomorov NYu, Gogoleva IV, et al. Study of the neuroregenerative effect of Cerebrolysin in traumatic brain injury. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2013;113(4): 57-60. (In Russ.).

52. Koren I, Reem E, Kimchi A. DAP1, a novel substrate of mTOR, negatively regulates autophagy. Curr Biol. 2010;22;20(12):1093-8. doi: 10.1016/j.cub.2010.04.041.

53. Yu Z, Zhou X, Wang W, et al. Dynamic phosphorylation of CENP-A at Ser68 orchestrates its cell-cycle-dependent deposition at centromeres. Dev Cell. 2015 Jan 12;32(1):68-81. doi: 10.1016/j.devcel.2014.11.030.

54. Marlier Q, Jibassia F, Verteneuil S, et al. Genetic and pharmacological inhibition of Cdk1 provides neuroprotection towards ischemic neuronal death. Cell Death Discov. 2018 Mar 16;4:43. doi: 10.1038/s41420-018-0044-7.

55. Blagosklonny MV. Rapamycin for longevity: opinion article. Aging (Albany NY). 2019 Oct 4; 11(19):8048-8067. doi: 10.18632/aging.102355. Epub 2019 Oct 4.

56. Masuda F, Ishii M, Mori A, et al. Glucose restriction induces transient G2 cell cycle arrest extending cellular chronological lifespan. Sci Rep. 2016 Jan 25;6:19629. doi: 10.1038/srep19629.

57. Numazaki M, Tominaga T, Toyooka H, Tominaga M. Direct phosphorylation of capsaicin receptor VR1 by protein kinase Cepsilon and identification of two target serine residues. J Biol Chem. 2002;277(16):13375-8. doi: 10.1074/jbc.C200104200.

58. Hu S, Xie Z, Onishi A, et al. Profiling the human protein-DNA interactome reveals ERK2 as a transcriptional repressor of interferon signaling. Cell. 2009;139(3):610-22. doi: 10.1016/j.cell.2009.08.037.

59. Wang S, Ge W, Harns C, et al. Ablation of toll-like receptor 4 attenuates aging-induced myocardial remodeling and contractile dysfunction through NCoRI-HDAC1- mediated regulation of autophagy. J Mol Cell Cardiol. 2018 Jun; 119:40-50. doi: 10.1016/j.yjmcc.2018.04.009. Epub 2018 Apr 13.

60. Chen CH, Wang WJ, Kuo JC, et al. Bidirectional signals transduced by DAPKERK interaction promote the apoptotic effect of DAPK. EMBO J. 2005 Jan 26;24(2):294-304. Epub 2004 Dec 16. doi: 10.1038/sj.emboj.7600510.

61. Ruan X, Arendshorst WJ. Role of protein kinase C in angiotensin II-induced renal vasoconstriction in genetically hypertensive rats. Am J Physiol. 1996 Jun;270(6 Pt 2):F945-52. doi: 10.1152/ajprenal.1996.270.6.F945.

62. Nandi S, Reinert LS, Hachem A, et al. Phosphorylation of MCT-1 by p44/42 MAPK is required for its stabilization in response to DNA damage. Oncogene. 2007 Apr 5;26(16): 2283-9. doi: 10.1038/sj.onc.1210030.

63. Uneda K, Wakui H, Maeda A, et al. Angiotensin II Type 1 Receptor-Associated Protein Regulates Kidney Aging and Lifespan Independent of Angiotensin. J Am Heart Assoc. 2017 Jul 27;6(8). pii: e006120. doi: 10.1161/JAHA.117.006120.

64. Fluhrer R, Friedlein A, Haass C, Walter J. Phosphorylation of presenilin 1 at the caspase recognition site regulates its proteolytic processing and the progression of apoptosis. J Biol Chem. 2004 Jan 16;279(3):1585-93. Epub 2003 Oct 22.

65. Steiner H, Romig H, Pesold B, et al. Amyloidogenic function of the Alzheimer's disease-associated presenilin 1 in the absence of endoproteolysis. Biochemistry. 1999 Nov 2; 38(44):14600-5. doi: 10.1021/bi9914210.

66. Marambaud P, Shioi J, Serban G, et al. A presenilin-1/gamma-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions. EMBO J. 2002 Apr 15;21(8):1948-56. doi: 10.1093/emboj/21.8.1948.

67. Torshin IYu, Gromova OA. Ekspertnyi analiz dannykh v molekulyarnoi farmakologii [Expert data analysis in molecular pharmacology]. Moscow: MTsNMO; 2012. 748 p

68. Dovey HF, John V, Anderson JP, et al. Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain. J Neurochem. 2001 Jan;76(1):173-81. doi: 10.1046/j.1471-4159.2001.00012.x.

69. Sadin AV, Zhidomorov NYu, Gogoleva IV, et al. Study of the neuroregenerative effect of Cerebrolysin in traumatic brain injury. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2013;113(4): 57-60. (In Russ.).

70. Ye J, Rawson RB, Komuro R, et al. ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol Cell. 2000 Dec;6(6):1355-64. doi: 10.1016/s1097-2765(00)00133-7.

71. Yu Z, Zhou X, Wang W, et al. Dynamic phosphorylation of CENP-A at Ser68 orchestrates its cell-cycle-dependent deposition at centromeres. Dev Cell. 2015 Jan 12;32(1):68-81. doi: 10.1016/j.devcel.2014.11.030.

72. He P, Lee SJ, Lin S, et al. Serum- and glucocorticoid-induced kinase 3 in recycling endosomes mediates acute activation of Na+/H+ exchanger NHE3 by glucocorticoids. Mol Biol Cell. 2011 Oct;22(20):3812-25. doi: 10.1091/mbc.E11-04-0328.

73. Marlier Q, Jibassia F, Verteneuil S, et al. Genetic and pharmacological inhibition of Cdk1 provides neuroprotection towards ischemic neuronal death. Cell Death Discov. 2018 Mar 16;4:43. doi: 10.1038/s41420-018-0044-7.

74. Masuda F, Ishii M, Mori A, et al. Glucose restriction induces transient G2 cell cycle arrest extending cellular chronological lifespan. Sci Rep. 2016 Jan 25;6:19629. doi: 10.1038/srep19629.

75. Yoo D, Kim BY, Campo C, et al. Cell surface expression of the ROMK (Kir 1.1) channel is regulated by the aldosterone-induced kinase, SGK-1, and protein kinase A. J Biol Chem. 2003 Jun 20;278(25):23066-75. doi: 10.1074/jbc.M212301200.

76. Hu S, Xie Z, Onishi A, et al. Profiling the human protein-DNA interactome reveals ERK2 as a transcriptional repressor of interferon signaling. Cell. 2009;139(3):610-22. doi: 10.1016/j.cell.2009.08.037.

77. Lee JM, Lee JS, Kim H, et al. EZH2 generates a methyl degron that is recognized by the DCAF1/DDB1/CUL4 E3 ubiquitin ligase complex. Mol Cell. 2012 Nov 30;48(4):572-86. doi: 10.1016/j.molcel.2012.09.004.

78. Tamori Y, Bialucha CU, Tian AG, et al. Involvement of Lgl and Mahjong/VprBP in cell competition. PLoS Biol. 2010 Jul 13;8(7): e1000422. doi: 10.1371/journal.pbio.1000422.

79. Chen CH, Wang WJ, Kuo JC, et al. Bidirectional signals transduced by DAPKERK interaction promote the apoptotic effect of DAPK. EMBO J. 2005 Jan 26;24(2):294-304. Epub 2004 Dec 16. doi: 10.1038/sj.emboj.7600510.

80. Voskresenskaya ON, Zakharov NB, Tarasova YuS, et al. Possible mechanisms of cognitive dysfunction in patients with chronic forms of cerebrovascular diseases. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2018;10(1):32-36. (In Russ.). doi: 10.14412/2074-2711-2018-1-32-36

81. Nandi S, Reinert LS, Hachem A, et al. Phosphorylation of MCT-1 by p44/42 MAPK is required for its stabilization in response to DNA damage. Oncogene. 2007 Apr 5;26(16): 2283-9. doi: 10.1038/sj.onc.1210030.

82. Gromova OA, Torshin IYu, Fedotova LE. Geriatric information analysis of the molecular properties of mexidole. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2017;9(4):46–54. (In Russ.). doi: 10.14412/2074-2711-2017-4-46-54.

83. Steiner H, Romig H, Pesold B, et al. Amyloidogenic function of the Alzheimer's disease-associated presenilin 1 in the absence of endoproteolysis. Biochemistry. 1999 Nov 2; 38(44):14600-5. doi: 10.1021/bi9914210.

84. Marambaud P, Shioi J, Serban G, et al. A presenilin-1/gamma-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions. EMBO J. 2002 Apr 15;21(8):1948-56. doi: 10.1093/emboj/21.8.1948.

85. Torshin IYu, Gromova OA, Fedotova LE, Gromov AN. Comparative chemoreactome analysis of dexketoprofen, ketoprofen, and diclofenac. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2018;10(1):47-54. (In Russ.). doi: 10.14412/2074-2711-2018-1-47-54.

86. Dovey HF, John V, Anderson JP, et al. Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain. J Neurochem. 2001 Jan;76(1):173-81. doi: 10.1046/j.1471-4159.2001.00012.x.

87. Ye J, Rawson RB, Komuro R, et al. ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol Cell. 2000 Dec;6(6):1355-64. doi: 10.1016/s1097-2765(00)00133-7.

88. He P, Lee SJ, Lin S, et al. Serum- and glucocorticoid-induced kinase 3 in recycling endosomes mediates acute activation of Na+/H+ exchanger NHE3 by glucocorticoids. Mol Biol Cell. 2011 Oct;22(20):3812-25. doi: 10.1091/mbc.E11-04-0328.

89. Yoo D, Kim BY, Campo C, et al. Cell surface expression of the ROMK (Kir 1.1) channel is regulated by the aldosterone-induced kinase, SGK-1, and protein kinase A. J Biol Chem. 2003 Jun 20;278(25):23066-75. doi: 10.1074/jbc.M212301200.

90. Lee JM, Lee JS, Kim H, et al. EZH2 generates a methyl degron that is recognized by the DCAF1/DDB1/CUL4 E3 ubiquitin ligase complex. Mol Cell. 2012 Nov 30;48(4):572-86. doi: 10.1016/j.molcel.2012.09.004.

91. Tamori Y, Bialucha CU, Tian AG, et al. Involvement of Lgl and Mahjong/VprBP in cell competition. PLoS Biol. 2010 Jul 13;8(7): e1000422. doi: 10.1371/journal.pbio.1000422.

92. Voskresenskaya ON, Zakharov NB, Tarasova YuS, et al. Possible mechanisms of cognitive dysfunction in patients with chronic forms of cerebrovascular diseases. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2018;10(1):32-36. (In Russ.). doi: 10.14412/2074-2711-2018-1-32-36

93. Gromova OA, Torshin IYu, Fedotova LE. Geriatric information analysis of the molecular properties of mexidole. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2017;9(4):46–54. (In Russ.). doi: 10.14412/2074-2711-2017-4-46-54.

94. Torshin IYu, Gromova OA, Fedotova LE, Gromov AN. Comparative chemoreactome analysis of dexketoprofen, ketoprofen, and diclofenac. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2018;10(1):47-54. (In Russ.). doi: 10.14412/2074-2711-2018-1-47-54.


For citation:


Gromova O.A., Torshin I.Y., Zgoda V.G., Sorokin A.I., Tikhonova O.V. Geroprotective properties of neuroprotective and neurotrophic peptides. Neurology, Neuropsychiatry, Psychosomatics. 2020;12(1):61-67. (In Russ.) https://doi.org/10.14412/2074-2711-2020-1-61-67

Views: 43


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2074-2711 (Print)
ISSN 2310-1342 (Online)