Hypericin as a potential drug for treating Alzheimer's disease and type 2 diabetes with a view to drug repositioning.
Alzheimer's disease
drug repositioning
hypericin
type 2 diabetes
Journal
CNS neuroscience & therapeutics
ISSN: 1755-5949
Titre abrégé: CNS Neurosci Ther
Pays: England
ID NLM: 101473265
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
revised:
25
04
2023
received:
15
02
2023
accepted:
29
04
2023
medline:
23
10
2023
pubmed:
15
5
2023
entrez:
15
5
2023
Statut:
ppublish
Résumé
Alzheimer's disease (AD) and type 2 diabetes (T2D) are two of the most common diseases in elderly population and they have a high rate of comorbidity. Study has revealed that T2D is a major risk factor of AD, and thus exploring therapeutic approaches that can target both diseases has drawn much interest in recent years. In this study, we tried to explore drugs that could be potentially used to prevent or treat both AD and T2D via a drug repositioning approach. We first searched the known drugs that may be effective to T2D treatment based on the network distance between the T2D-associated genes and drugs deposited in the DrugBank database. Then, via molecular docking, we further screened these drugs by examining their interaction with islet amyloid polypeptide (IAPP) and Aβ42 peptide, the key components involved in the pathogenesis of T2D or AD. Finally, the binding between the selected drug candidates and the target proteins was verified by molecular dynamics (MD) simulation; and the potential function of the drug candidates and the corresponding targets were analyzed. From multiple resources, 734 T2D-associated genes were collected, and a list of 1109 drug candidates for T2D was obtained. We found that hypericin had the lowest binding energy and the most stable interaction with either IAPP or Aβ42 peptide. In addition, we also found that the target genes regulated by hypericin were differentially expressed in the tissues related to the two diseases. Our results show that hypericin may be able to bind with IAPP and Aβ42 stably and prevent their accumulation, and thus could be a promising drug candidate for treating the comorbidity of AD and T2D.
Identifiants
pubmed: 37183545
doi: 10.1111/cns.14260
pmc: PMC10580347
doi:
Substances chimiques
hypericin
7V2F1075HD
Islet Amyloid Polypeptide
0
Amyloid beta-Peptides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3307-3321Informations de copyright
© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.
Références
Lancet. 2017 Jun 3;389(10085):2239-2251
pubmed: 28190580
Cancer Res. 2003 Nov 15;63(22):8062-8
pubmed: 14633740
Free Radic Biol Med. 2014 Feb;67:292-303
pubmed: 24269898
JAMA. 2021 Apr 27;325(16):1640-1649
pubmed: 33904867
Physiol Rev. 2011 Jul;91(3):795-826
pubmed: 21742788
Proteins. 2010 Jun;78(8):1950-8
pubmed: 20408171
Biochem Pharmacol. 2001 Oct 15;62(8):1059-70
pubmed: 11597574
Lancet. 2018 Nov 10;392(10159):1736-1788
pubmed: 30496103
J Chem Theory Comput. 2008 Mar;4(3):435-47
pubmed: 26620784
Drug Discov Today. 2022 Apr;27(4):1027-1043
pubmed: 35121174
Fitoterapia. 2014 Jan;92:23-33
pubmed: 24125916
Eur Biophys J. 2010 Oct;39(11):1493-501
pubmed: 20473492
Nucleic Acids Res. 2017 Jan 4;45(D1):D877-D887
pubmed: 27899610
Alzheimers Dement. 2014 Feb;10(1 Suppl):S26-32
pubmed: 24529521
J Am Geriatr Soc. 2012 May;60(5):916-21
pubmed: 22458300
Diabetes. 2016 Sep;65(9):2772-83
pubmed: 27335231
Alzheimers Dement. 2018 Feb;14(2):215-229
pubmed: 28923553
Amyloid. 2007 Jun;14(2):119-31
pubmed: 17577685
Handb Clin Neurol. 2019;167:231-255
pubmed: 31753135
Diabetes. 2014 Jul;63(7):2253-61
pubmed: 24931035
Nat Rev Neurol. 2016 Jan;12(1):15-27
pubmed: 26635213
Brief Bioinform. 2021 May 20;22(3):
pubmed: 32778891
Alzheimer Dis Assoc Disord. 2017 Apr-Jun;31(2):107-113
pubmed: 28538088
Curr Med Chem. 2021;28(23):4638-4669
pubmed: 33138749
Chem Biol Interact. 2010 Oct 6;188(1):59-65
pubmed: 20637187
Nucleic Acids Res. 2021 Jan 8;49(D1):D1144-D1151
pubmed: 33237278
Front Aging Neurosci. 2021 Feb 12;13:631770
pubmed: 33643025
Neurology. 2022 Aug 16;99(7):e650-e659
pubmed: 35654594
Comput Struct Biotechnol J. 2022 Jun 01;20:2839-2847
pubmed: 35765655
Mini Rev Med Chem. 2021;21(9):1144-1149
pubmed: 32718290
Nucleic Acids Res. 2021 Jan 8;49(D1):D1138-D1143
pubmed: 33068428
Alzheimers Dement (Amst). 2021 Nov 10;13(1):e12248
pubmed: 34796262
Int J Biol Sci. 2019 Jun 2;15(7):1472-1487
pubmed: 31337977
Neuropharmacology. 2018 Jul 1;136(Pt B):251-259
pubmed: 29402504
Lancet Neurol. 2020 Sep;19(9):758-766
pubmed: 32730766
Nucleic Acids Res. 2021 Jan 8;49(D1):D1413-D1419
pubmed: 33010177
Curr Alzheimer Res. 2019;16(8):741-752
pubmed: 31518224
J Comput Chem. 2008 Apr 15;29(5):673-85
pubmed: 17849388
Bioinformatics. 2020 Nov 1;36(17):4626-4632
pubmed: 32516365
J Comput Chem. 2009 Dec;30(16):2785-91
pubmed: 19399780
Lancet Diabetes Endocrinol. 2020 Sep;8(9):736-738
pubmed: 32738930
Diabetes. 2004 Feb;53(2):474-81
pubmed: 14747300
Biomed Pharmacother. 2019 Jan;109:2173-2181
pubmed: 30551474
J Alzheimers Dis. 2019;72(s1):S71-S79
pubmed: 31744006
Genes (Basel). 2020 Oct 16;11(10):
pubmed: 33081197
J Alzheimers Dis. 2018;63(2):773-781
pubmed: 29660933
Mini Rev Med Chem. 2016;16(9):710-20
pubmed: 26156546
Curr Alzheimer Res. 2013 Dec;10(10):1057-69
pubmed: 24156265
Diabetologia. 2016 Jul;59(7):1513-1523
pubmed: 27138913
Neuromolecular Med. 2002;2(3):299-309
pubmed: 12622408
Int J Biochem Cell Biol. 2008;40(8):1509-21
pubmed: 18226577
Biochem Biophys Res Commun. 2016 Dec 2;481(1-2):71-76
pubmed: 27825966
J Clin Endocrinol Metab. 2020 Apr 1;105(4):
pubmed: 31778170
J Clin Invest. 2012 Apr;122(4):1316-38
pubmed: 22476197
Nat Rev Neurosci. 2016 Jan;17(1):5-21
pubmed: 26631930
Bioinformatics. 2006 Nov 1;22(21):2695-6
pubmed: 16940322
J Pharm Anal. 2022 Aug;12(4):556-569
pubmed: 36105173
BMC Res Notes. 2012 Jul 23;5:367
pubmed: 22824207
Prog Neuropsychopharmacol Biol Psychiatry. 2017 Oct 3;79(Pt B):77-83
pubmed: 28583443
J Pharmacol Exp Ther. 2000 Jul;294(1):88-95
pubmed: 10871299
J Alzheimers Dis. 2018;65(4):1225-1236
pubmed: 30149446
Molecules. 2021 Jul 28;26(15):
pubmed: 34361714
Life Sci. 2016 Jan 1;144:30-6
pubmed: 26612349
Bioessays. 2018 Jun;40(6):e1800061
pubmed: 29696673
Photodiagnosis Photodyn Ther. 2015 Sep;12(3):490-503
pubmed: 26003114
J Comput Chem. 2010 Jan 30;31(2):455-61
pubmed: 19499576
Int J Mol Sci. 2020 Oct 30;21(21):
pubmed: 33143088
Compr Physiol. 2020 Jul 8;10(3):811-837
pubmed: 32941692
Am J Alzheimers Dis Other Demen. 2020 Jan-Dec;35:1533317519899546
pubmed: 32162525
Antioxidants (Basel). 2021 Jul 05;10(7):
pubmed: 34356309
Curr Pharm Des. 2005;11(2):233-53
pubmed: 15638760
Nat Struct Mol Biol. 2020 Jul;27(7):660-667
pubmed: 32541895
World J Diabetes. 2021 Jun 15;12(6):745-766
pubmed: 34168725
Toxicol In Vitro. 2014 Oct;28(7):1259-73
pubmed: 24994473
Eur Neuropsychopharmacol. 2014 Dec;24(12):1954-60
pubmed: 25088942
J Cell Physiol. 2022 Jul;237(7):2838-2861
pubmed: 35580144
Int J Nanomedicine. 2019 Jul 19;14:5541-5554
pubmed: 31410002
J Diabetes Res. 2017;2017:7420796
pubmed: 28656154
Alzheimers Dement. 2017 Feb;13(2):111-118
pubmed: 27793691
Dialogues Clin Neurosci. 2019 Mar;21(1):83-91
pubmed: 31607783
CNS Neurosci Ther. 2023 Nov;29(11):3307-3321
pubmed: 37183545
Phytomedicine. 2022 Oct;105:154356
pubmed: 35985181
Pharm Res. 2022 Jun;39(6):1233-1248
pubmed: 35650449
Nucleic Acids Res. 2020 Jan 8;48(D1):D845-D855
pubmed: 31680165
Biol Chem. 2020 Sep 04;402(2):133-153
pubmed: 33544470
Rev Prat. 2020 Feb;70(2):149-151
pubmed: 32877124
J Chem Inf Model. 2014 Jul 28;54(7):1951-62
pubmed: 24850022
J Alzheimers Dis. 2018;62(3):1381-1390
pubmed: 29562538
Ageing Res Rev. 2019 Sep;54:100936
pubmed: 31330313
J Mol Graph Model. 2021 Dec;109:108027
pubmed: 34534891
Nature. 2004 Apr 1;428(6982):493-521
pubmed: 15057822
J Alzheimers Dis. 2017;59(2):421-432
pubmed: 28269785
Biochemistry. 2004 Oct 12;43(40):12761-9
pubmed: 15461448
FEBS Lett. 2008 Oct 15;582(23-24):3288-92
pubmed: 18805418
J Clin Neurosci. 2020 Nov;81:234-239
pubmed: 33222922
Int J Mol Sci. 2018 Oct 24;19(11):
pubmed: 30355995
Pharm Biol. 2017 Dec;55(1):906-911
pubmed: 28147885
Front Neurosci. 2018 Jun 08;12:383
pubmed: 29950970