Autophagic flux is impaired in the brain tissue of Tay-Sachs disease mouse model.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2023
2023
Historique:
received:
03
04
2022
accepted:
05
01
2023
entrez:
17
3
2023
pubmed:
18
3
2023
medline:
22
3
2023
Statut:
epublish
Résumé
Tay-Sachs disease is a lethal lysosomal storage disorder caused by mutations in the HexA gene encoding the α subunit of the lysosomal β-hexosaminidase enzyme (HEXA). Abnormal GM2 ganglioside accumulation causes progressive deterioration in the central nervous system in Tay-Sachs patients. Hexa-/- mouse model failed to display abnormal phenotype. Recently, our group generated Hexa-/-Neu3-/- mouse showed severe neuropathological indications similar to Tay-Sachs patients. Despite excessive GM2 ganglioside accumulation in the brain and visceral organs, the regulation of autophagy has not been clarified yet in the Tay-Sachs disease mouse model. Therefore, we investigated distinct steps of autophagic flux using markers including LC3 and p62 in four different brain regions from the Hexa-/-Neu3-/- mice model of Tay-Sachs disease. Our data revealed accumulated autophagosomes and autophagolysosomes indicating impairment in autophagic flux in the brain. We suggest that autophagy might be a new therapeutic target for the treatment of devastating Tay-Sachs disease.
Identifiants
pubmed: 36928510
doi: 10.1371/journal.pone.0280650
pii: PONE-D-22-09806
pmc: PMC10019743
doi:
Substances chimiques
beta-N-Acetylhexosaminidases
EC 3.2.1.52
G(M2) Ganglioside
19600-01-2
Hexosaminidase A
EC 3.2.1.52
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0280650Informations de copyright
Copyright: © 2023 Sengul et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Nat Rev Mol Cell Biol. 2020 Feb;21(2):101-118
pubmed: 31768005
Autophagy. 2012 May 1;8(5):719-30
pubmed: 22647656
Autophagy. 2008 Jan;4(1):113-4
pubmed: 18000397
Exp Neurol. 2018 Jan;299(Pt A):26-41
pubmed: 28974375
Autophagy. 2012 Apr;8(4):445-544
pubmed: 22966490
Angew Chem Int Ed Engl. 1999 Jun 1;38(11):1532-1568
pubmed: 29710982
Neurosci Lett. 2021 Sep 25;762:136155
pubmed: 34358625
Biochim Biophys Acta. 2008 Mar;1780(3):421-33
pubmed: 17991443
Nature. 2000 Aug 24;406(6798):902-6
pubmed: 10972293
Autophagy. 2010 Jul;6(5):589-99
pubmed: 20431343
Mol Genet Metab. 2009 Dec;98(4):393-9
pubmed: 19656701
Neurochem Res. 2012 Jun;37(6):1185-91
pubmed: 22488331
Br J Pharmacol. 2010 Feb 1;159(3):586-603
pubmed: 20067473
PLoS Biol. 2013;11(3):e1001506
pubmed: 23554574
Methods Enzymol. 2009;452:181-97
pubmed: 19200883
Autophagy. 2014 May;10(5):750-65
pubmed: 24589479
J Neuroinflammation. 2020 Sep 20;17(1):277
pubmed: 32951593
Autophagy. 2010 Jul;6(5):648-9
pubmed: 20458183
Am J Pathol. 2002 Jan;160(1):255-63
pubmed: 11786419
Am J Pathol. 2007 Sep;171(3):962-75
pubmed: 17631520
Neurobiol Dis. 2019 Sep;129:195-207
pubmed: 31108173
Cell Res. 2014 Jan;24(1):24-41
pubmed: 24366339
Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9975-9
pubmed: 7937929
Acta Pharmacol Sin. 2021 Apr;42(4):518-528
pubmed: 32724177
Autophagy. 2007 Sep-Oct;3(5):487-9
pubmed: 17611388
Hum Mol Genet. 2008 Dec 15;17(24):3897-908
pubmed: 18782848
Glycoconj J. 2014 Dec;31(9):613-22
pubmed: 25351657
Ann Neurol. 2006 Apr;59(4):700-8
pubmed: 16532490
Hum Mol Genet. 2008 Sep 1;17(17):2723-37
pubmed: 18550655
J Cell Biol. 2005 Nov 21;171(4):603-14
pubmed: 16286508
Biochem Biophys Res Commun. 2008 Mar 14;367(3):616-22
pubmed: 18190792
Hum Mol Genet. 1996 Jan;5(1):1-14
pubmed: 8789434
FEBS Lett. 2010 May 3;584(9):1741-7
pubmed: 19822144
J Biol Chem. 2006 Dec 22;281(51):39041-50
pubmed: 17056595