Rational design and synthesis of a novel BODIPY-based probe for selective imaging of tau tangles in human iPSC-derived cortical neurons.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
28 03 2022
28 03 2022
Historique:
received:
26
11
2021
accepted:
15
03
2022
entrez:
29
3
2022
pubmed:
30
3
2022
medline:
5
4
2022
Statut:
epublish
Résumé
Numerous studies have shown a strong correlation between the number of neurofibrillary tangles of the tau protein and Alzheimer's disease progression, making the quantitative detection of tau very promising from a clinical point of view. However, the lack of highly reliable fluorescent probes for selective imaging of tau neurofibrillary tangles is a major challenge due to sharing similar β-sheet motifs with homologous Amyloid-β fibrils. In the current work, we describe the rational design and the in silico evaluation of a small-size focused library of fluorescent probes, consisting of a BODIPY core (electron acceptor) featuring highly conjugated systems (electron donor) with a length in the range 13-19 Å at C3. Among the most promising probes in terms of binding mode, theoretical affinity and polarity, BT1 has been synthesized and tested in vitro onto human induced pluripotent stem cells derived neuronal cell cultures. The probe showed excellent photophysical properties and high selectivity allowing in vitro imaging of hyperphosphorylated tau protein filaments with minimal background noise. Our findings offer new insight into the structure-activity relationship of this class of tau selective fluorophores, paving the way for boosting tau tangle detection in patients possibly through retinal spectral scans.
Identifiants
pubmed: 35347170
doi: 10.1038/s41598-022-09016-z
pii: 10.1038/s41598-022-09016-z
pmc: PMC8960764
doi:
Substances chimiques
4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
0
Boron Compounds
0
tau Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5257Subventions
Organisme : European Research Council
ID : Synergy grant ASTRA 855923
Pays : International
Informations de copyright
© 2022. The Author(s).
Références
Alzheimers Dement. 2018 Apr;14(4):535-562
pubmed: 29653606
Nat Methods. 2013 Jun;10(6):553-6
pubmed: 23584186
Dis Model Mech. 2015 Jul 1;8(7):755-66
pubmed: 26035390
ACS Chem Neurosci. 2017 Oct 18;8(10):2124-2131
pubmed: 28737890
Cell Death Dis. 2018 Jun 7;9(6):685
pubmed: 29880901
Cold Spring Harb Perspect Biol. 2017 May 1;9(5):
pubmed: 27940517
PLoS Comput Biol. 2009 Mar;5(3):e1000333
pubmed: 19325876
Nat Rev Dis Primers. 2015 Oct 15;1:15056
pubmed: 27188934
Chem Commun (Camb). 2018 Oct 11;54(82):11558-11561
pubmed: 30204164
Front Neurosci. 2019 Sep 04;13:925
pubmed: 31551688
ACS Sens. 2021 Jun 25;6(6):2281-2289
pubmed: 34115933
Drug Discov Today Technol. 2013 Sep;10(3):e319-27
pubmed: 24050129
Org Biomol Chem. 2015 Dec 14;13(46):11194-9
pubmed: 26488450
Chem Commun (Camb). 2018 Aug 2;54(63):8717-8720
pubmed: 30023996
Lancet Neurol. 2016 Jun;15(7):673-684
pubmed: 27068280
Nature. 2017 Jul 13;547(7662):185-190
pubmed: 28678775
Biophys Chem. 2004 Feb 1;107(2):175-87
pubmed: 14962598
Nat Methods. 2017 Feb 13;14(4):399-402
pubmed: 28192420
Arch Biochem Biophys. 2011 Apr 1;508(1):13-24
pubmed: 21303653
ACS Chem Neurosci. 2016 Nov 16;7(11):1474-1481
pubmed: 27576176
Arch Neurol. 2012 Feb;69(2):198-207
pubmed: 21987394
Eur J Med Chem. 2018 Jan 20;144:651-661
pubmed: 29289888
Front Mol Neurosci. 2020 Dec 15;13:586169
pubmed: 33384582
Nat Neurosci. 2013 Jul;16(7):780-9
pubmed: 23799470
Annu Rev Med. 2017 Jan 14;68:413-430
pubmed: 28099083
Acta Neuropathol. 1992;84(6):596-605
pubmed: 1281953
J Comput Chem. 2009 Dec;30(16):2785-91
pubmed: 19399780
Neural Regen Res. 2022 Feb;17(2):330-332
pubmed: 34269204
Eur J Pharmacol. 2019 Aug 5;856:172415
pubmed: 31132354
Med Chem. 2018;14(1):34-43
pubmed: 28969570
Neuron. 2013 Jun 5;78(5):785-98
pubmed: 23764284
Science. 2002 Jul 19;297(5580):353-6
pubmed: 12130773
ACS Cent Sci. 2019 Feb 27;5(2):209-217
pubmed: 30834309
FASEB J. 2012 May;26(5):1946-59
pubmed: 22253473
J Am Chem Soc. 2017 Sep 27;139(38):13393-13403
pubmed: 28857559
Cell Death Dis. 2021 May 15;12(5):498
pubmed: 33993189
Front Neurosci. 2020 Jun 17;14:655
pubmed: 32625060
Neurology. 2007 Feb 13;68(7):501-8
pubmed: 17065593
Curr Opin Neurobiol. 2016 Feb;36:43-51
pubmed: 26397020
N Engl J Med. 2014 Jan 23;370(4):311-21
pubmed: 24450890
Ann Neurol. 1998 Feb;43(2):193-204
pubmed: 9485060
Alzheimers Dement (Amst). 2017 Nov 06;10:49-55
pubmed: 29201990
Science. 2018 Jun 15;360(6394):1242-1246
pubmed: 29748322
Neurol Ther. 2019 Dec;8(Suppl 2):57-72
pubmed: 31833024
Neurosci Lett. 1995 Apr 21;189(3):167-9
pubmed: 7624036
Chem Soc Rev. 2018 Apr 3;47(7):2249-2265
pubmed: 29484335
J Am Chem Soc. 2009 Oct 28;131(42):15257-61
pubmed: 19807070
Nat Rev Neurol. 2013 Dec;9(12):677-86
pubmed: 24217510
J Chem Inf Model. 2010 Apr 26;50(4):572-84
pubmed: 20235588
Arch Neurol. 2008 Jan;65(1):45-53
pubmed: 17998437
Mol Psychiatry. 2019 Aug;24(8):1112-1134
pubmed: 30635637
PLoS One. 2012;7(12):e53547
pubmed: 23300938
N Engl J Med. 2014 Jan 23;370(4):322-33
pubmed: 24450891
Neural Regen Res. 2022 Feb;17(2):333-335
pubmed: 34269205
Neuroimage Clin. 2013 Mar 05;2:356-65
pubmed: 24179789
Neuron. 2003 Jul 31;39(3):409-21
pubmed: 12895417
Curr Opin Chem Biol. 2010 Feb;14(1):71-9
pubmed: 19879798
Prog Retin Eye Res. 2021 May;82:100899
pubmed: 32890742