STXBP1 encephalopathies: Clinical spectrum, disease mechanisms, and therapeutic strategies.
Munc18-1
STXBP1
encephalopathy
epilepsy
synapse
therapeutic approaches
Journal
Journal of neurochemistry
ISSN: 1471-4159
Titre abrégé: J Neurochem
Pays: England
ID NLM: 2985190R
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
revised:
24
06
2020
received:
23
04
2020
accepted:
30
06
2020
pubmed:
10
7
2020
medline:
22
6
2021
entrez:
10
7
2020
Statut:
ppublish
Résumé
Mutations in Munc18-1/STXBP1 (syntaxin-binding protein 1) are linked to various severe early epileptic encephalopathies and neurodevelopmental disorders. Heterozygous mutations in the STXBP1 gene include missense, nonsense, frameshift, and splice site mutations, as well as intragenic deletions and duplications and whole-gene deletions. No genotype-phenotype correlation has been identified so far, and patients are treated by anti-epileptic drugs because of the lack of a specific disease-modifying therapy. The molecular disease mechanisms underlying STXBP1-linked disorders are yet to be fully understood, but both haploinsufficiency and dominant-negative mechanisms have been proposed. This review focuses on the current understanding of the phenotypic spectrum of STXBP1-linked disorders, as well as discusses disease mechanisms in the context of the numerous pathways in which STXBP1 functions in the brain. We additionally evaluate the available animal models to study these disorders and highlight potential therapeutic approaches for treating these devastating diseases.
Identifiants
pubmed: 32643187
doi: 10.1111/jnc.15120
pmc: PMC7812771
mid: NIHMS1660710
doi:
Substances chimiques
Anticonvulsants
0
Munc18 Proteins
0
STXBP1 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
165-178Subventions
Organisme : NINDS NIH HHS
ID : R01-NS113960
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS102181
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS113960
Pays : United States
Organisme : Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD PhD Program
ID : T32GM007739
Organisme : NINDS NIH HHS
ID : R01-NS102181
Pays : United States
Informations de copyright
© 2020 International Society for Neurochemistry.
Références
Epilepsia. 2005;46 Suppl 9:57-66
pubmed: 16302876
Brain Dev. 2002 Jan;24(1):13-23
pubmed: 11751020
Neuron. 1997 Mar;18(3):453-61
pubmed: 9115738
Lancet. 2012 Nov 10;380(9854):1674-82
pubmed: 23020937
Clin Genet. 2012 Apr;81(4):399-402
pubmed: 22211739
Dev Med Child Neurol. 2011 Sep;53(9):806-807
pubmed: 21631463
Nature. 2013 Sep 12;501(7466):217-21
pubmed: 23934111
Science. 1997 Jun 27;276(5321):2045-7
pubmed: 9197268
Neurology. 2019 Jul 16;93(3):114-123
pubmed: 31221716
J Cell Biol. 2009 Mar 9;184(5):751-64
pubmed: 19255244
Ann Neurol. 2009 Jun;65(6):748-53
pubmed: 19557857
J Clin Invest. 2015 Sep;125(9):3560-71
pubmed: 26280581
Nat Commun. 2017 Jun 21;8:15915
pubmed: 28635948
Mol Cell. 2004 Jan 30;13(2):157-68
pubmed: 14759362
J Cell Sci. 2007 Dec 15;120(Pt 24):4407-15
pubmed: 18057031
Elife. 2014 Sep 23;3:e03640
pubmed: 25247702
Stem Cell Res. 2019 Aug;39:101485
pubmed: 31255830
J Child Neurol. 2014 Feb;29(2):249-53
pubmed: 24170257
Expert Opin Ther Targets. 2017 Nov;21(11):1027-1036
pubmed: 28971703
J Neurochem. 2006 May;97(3):818-33
pubmed: 16515538
Mol Neurodegener. 2020 Jan 22;15(1):1
pubmed: 31964406
Proc Natl Acad Sci U S A. 2018 Jun 12;115(24):E5605-E5613
pubmed: 29844163
EMBO J. 2012 May 2;31(9):2156-68
pubmed: 22446389
J Neurochem. 1992 Apr;58(4):1517-25
pubmed: 1347782
Biochem J. 2008 Jan 15;409(2):407-16
pubmed: 17919117
Eur J Neurosci. 1999 Dec;11(12):4262-8
pubmed: 10594652
J Neurosci. 1997 Nov 1;17(21):8061-73
pubmed: 9334382
Eur J Paediatr Neurol. 2020 Jan;24:15-23
pubmed: 31882278
Yeast. 1991 Aug-Sep;7(6):643-50
pubmed: 1767592
Nat Chem Biol. 2014 Jun;10(6):443-9
pubmed: 24747528
Epilepsy Behav. 2019 Mar;92:121-124
pubmed: 30654231
J Child Neurol. 2015 Apr;30(5):622-4
pubmed: 23533165
Cell. 2007 Jan 12;128(1):183-95
pubmed: 17218264
Ther Adv Neurol Disord. 2018 May 23;11:1756286418776932
pubmed: 29854003
Nature. 1997 Aug 28;388(6645):839-40
pubmed: 9278044
Behav Brain Res. 2014 Mar 1;260:44-52
pubmed: 24304718
Proc Natl Acad Sci U S A. 2016 Oct 25;113(43):12280-12285
pubmed: 27791016
Neuron. 2018 Jun 6;98(5):977-991.e5
pubmed: 29754754
Cereb Cortex. 2000 Oct;10(10):981-91
pubmed: 11007549
Medicine (Baltimore). 2018 May;97(18):e0663
pubmed: 29718889
Pediatr Neurol. 2017 Dec;77:61-66
pubmed: 29056246
J Neurochem. 2005 Jun;93(6):1393-400
pubmed: 15935055
Handb Clin Neurol. 2013;111:611-8
pubmed: 23622208
Mol Genet Genomic Med. 2017 Jun 20;5(5):495-507
pubmed: 28944233
Cell Mol Life Sci. 2008 Sep;65(18):2801-13
pubmed: 18726178
J Biol Chem. 2014 Nov 28;289(48):33617-28
pubmed: 25326390
Neurogenetics. 2015 Jan;16(1):65-7
pubmed: 25418441
Science. 2015 Sep 4;349(6252):1111-4
pubmed: 26339030
Prion. 2014 Mar-Apr;8(2):
pubmed: 24818993
Brain. 2020 Feb 1;143(2):441-451
pubmed: 31855252
Nature. 1993 Nov 25;366(6453):347-51
pubmed: 8247129
Hum Genet. 2018 Sep;137(9):735-752
pubmed: 30167849
Epilepsia. 2016 Apr;57(4):e81-6
pubmed: 26918652
Hum Mol Genet. 2017 Dec 15;26(24):4961-4974
pubmed: 29040524
J Neurosci. 2004 Jul 21;24(29):6629-37
pubmed: 15269275
J Biol Chem. 2007 Apr 20;282(16):12097-103
pubmed: 17264080
Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2697-702
pubmed: 17301226
JAMA Pediatr. 2017 Sep 1;171(9):863-871
pubmed: 28759667
Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12593-8
pubmed: 8901627
Epilepsia. 2010 Dec;51(12):2449-52
pubmed: 21204804
Eur J Paediatr Neurol. 2016 Jul;20(4):661-5
pubmed: 27184330
Epilepsia. 2013 May;54(5):e74-80
pubmed: 23409955
Neuron. 2001 Aug 30;31(4):581-91
pubmed: 11545717
EMBO J. 2008 Apr 9;27(7):923-33
pubmed: 18337752
Mol Med. 2018 May 29;24(1):25
pubmed: 30134808
J Cell Sci. 2015 Dec 1;128(23):4279-92
pubmed: 26483382
Eur J Hum Genet. 2011 May;19(5):607-9
pubmed: 21364700
Mol Cell Neurosci. 2018 Apr;88:33-42
pubmed: 29217410
J Biol Chem. 2004 May 28;279(22):23740-7
pubmed: 15033971
Cell. 2010 Apr 30;141(3):524-35
pubmed: 20434989
EMBO J. 1998 Jan 2;17(1):127-39
pubmed: 9427747
Neurology. 2017 Aug 29;89(9):893-899
pubmed: 28733343
N Engl J Med. 1996 Sep 19;335(12):855-9
pubmed: 8778603
Drugs R D. 2011 Sep 1;11(3):227-49
pubmed: 21902286
Front Mol Neurosci. 2019 Dec 17;12:306
pubmed: 31920537
PLoS One. 2016 Mar 10;11(3):e0151148
pubmed: 26963117
Epileptic Disord. 2013 Mar;15(1):55-61
pubmed: 23531706
Turk J Pediatr. 2019;61(5):757-759
pubmed: 32105008
Nucleic Acids Res. 2015 Mar 31;43(6):3298-308
pubmed: 25735746
Neuroscience. 2020 Mar 1;429:203-212
pubmed: 31962145
Nat Struct Mol Biol. 2011 May;18(5):542-9
pubmed: 21499244
J Med Genet. 2016 Mar;53(3):190-9
pubmed: 26740508
Mol Biol Cell. 2008 Dec;19(12):5422-34
pubmed: 18829865
Cell. 2011 Oct 28;147(3):666-77
pubmed: 22036572
Elife. 2018 Dec 12;7:
pubmed: 30540253
J Neurosci. 2017 Sep 6;37(36):8797-8815
pubmed: 28821673
Nat Commun. 2019 Jan 8;10(1):69
pubmed: 30622273
Genetics. 1974 May;77(1):71-94
pubmed: 4366476
J Neurosci. 2007 Nov 7;27(45):12147-55
pubmed: 17989281
Neuron. 2011 Apr 28;70(2):244-51
pubmed: 21521611
Brain. 2018 May 1;141(5):1350-1374
pubmed: 29538625
Proc Natl Acad Sci U S A. 2013 Jul 30;110(31):12637-42
pubmed: 23858467
J Cell Biol. 2016 Sep 12;214(6):705-18
pubmed: 27597756
Nature. 1994 Jun 9;369(6480):493-7
pubmed: 7911226
J Biol Chem. 2014 Apr 4;289(14):9639-50
pubmed: 24532794
Neuroreport. 2015 Mar 25;26(5):254-7
pubmed: 25714420
J Neurosci. 2017 Apr 26;37(17):4525-4539
pubmed: 28348137
Development. 1993 Apr;117(4):1309-19
pubmed: 8404533
Proc Natl Acad Sci U S A. 2010 Dec 28;107(52):22399-406
pubmed: 21139055
Int J Mol Sci. 2019 Jul 24;20(15):
pubmed: 31344879
J Cell Biol. 2014 Mar 3;204(5):759-75
pubmed: 24590174
Pediatr Neurol. 2012 Nov;47(5):317-23
pubmed: 23044011
Epilepsia. 2020 Apr;61(4):810-821
pubmed: 32112430
N Engl J Med. 2012 Nov 15;367(20):1921-9
pubmed: 23033978
PLoS One. 2006 Dec 27;1:e126
pubmed: 17205130
Ann Hum Genet. 2015 May;79(3):209-17
pubmed: 25779878
Annu Rev Cell Dev Biol. 2012;28:279-308
pubmed: 23057743
Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1409-14
pubmed: 12547917
Front Mol Neurosci. 2014 Feb 04;7:6
pubmed: 24550774
J Biol Chem. 1997 Dec 12;272(50):31459-64
pubmed: 9395480
Brain Dev. 2018 Jun;40(6):493-497
pubmed: 29544889
Neurology. 2010 Sep 28;75(13):1159-65
pubmed: 20876469
J Neurodev Disord. 2019 Aug 6;11(1):17
pubmed: 31387522
Nat Genet. 2008 Jun;40(6):782-8
pubmed: 18469812
Eur J Med Genet. 2013 Dec;56(12):683-5
pubmed: 24095819
J Biol Chem. 2000 Dec 22;275(51):39803-6
pubmed: 11036064
J Neurosci. 2016 Jun 29;36(26):6881-91
pubmed: 27358447
Epilepsia. 2015 Dec;56(12):1931-40
pubmed: 26514728
Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1445-9
pubmed: 8108429
Neurology. 2001 Jun 12;56(11):1445-52
pubmed: 11402099
Neurology. 2014 Apr 8;82(14):1245-53
pubmed: 24623842
Science. 2007 Feb 23;315(5815):1143-7
pubmed: 17289941
Neuron. 2013 Feb 6;77(3):542-58
pubmed: 23395379
Ont Health Technol Assess Ser. 2020 Mar 6;20(11):1-178
pubmed: 32194879
Handb Clin Neurol. 2013;111:627-33
pubmed: 23622210
J Neurosci. 2016 Jan 13;36(2):561-76
pubmed: 26758845
Genet Med. 2012 Oct;14(10):868-76
pubmed: 22722545
Nat Commun. 2018 Sep 28;9(1):3986
pubmed: 30266908
Epilepsia. 2010 Dec;51(12):2397-405
pubmed: 20887364
Neuron. 2015 Apr 22;86(2):442-56
pubmed: 25843403
Brain Dev. 2016 Jan;38(1):128-31
pubmed: 26212315
Science. 2000 Feb 4;287(5454):864-9
pubmed: 10657302
Cell Rep. 2018 Jun 5;23(10):2955-2966
pubmed: 29874582
Neurology. 2016 Mar 8;86(10):954-62
pubmed: 26865513
CNS Drugs. 2013 Mar;27(3):175-84
pubmed: 23397290
Science. 2010 Mar 26;327(5973):1614-8
pubmed: 20150444
Elife. 2017 May 06;6:
pubmed: 28477408
Seizure. 2018 Aug;60:68-70
pubmed: 29929108
J Child Neurol. 2012 Jun;27(6):811-4
pubmed: 22596016
Neuron. 1994 Sep;13(3):555-66
pubmed: 7917291
J Neurosci. 2006 Dec 13;26(50):13089-101
pubmed: 17167098
Am J Med Genet A. 2015 Sep;167A(9):2017-25
pubmed: 25914188
NCHS Data Brief. 2017 Nov;(291):1-8
pubmed: 29235982
Epilepsy Res. 2006 Aug;70 Suppl 1:S58-67
pubmed: 16829045
Elife. 2020 Feb 19;9:
pubmed: 32073399
PLoS One. 2015 May 07;10(5):e0126446
pubmed: 25951140
Acta Neuropathol Commun. 2017 Nov 30;5(1):92
pubmed: 29191246
Cell Rep. 2014 Oct 9;9(1):206-218
pubmed: 25284778
Nature. 2000 Mar 23;404(6776):355-62
pubmed: 10746715