Activation of ABCC1 transporter ameliorates synaptic dysregulation in Tay-Sachs disease neuron

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Activation of ABCC1 transporter ameliorates synaptic dysregulation in Tay-Sachs disease neuron
Συγγραφείς: Yumeng Zhang, Tadahiro Numakawa, Ryutaro Kajihara, Kiseok Lee, Jing Pu, Chisato Horita, Jun Kido, Muneaki Matsuo, Takumi Era
Πηγή: Neurobiology of Disease, Vol 216, Iss , Pp 107099- (2025)
Στοιχεία εκδότη: Elsevier, 2025.
Έτος έκδοσης: 2025
Συλλογή: LCC:Neurosciences. Biological psychiatry. Neuropsychiatry
Θεματικοί όροι: Tay-sachs disease, GM2 ganglioside, Ca2+ influx, Synaptic function, ABCC1 transporter, Thiethylperazine, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Περιγραφή: Tay-Sachs disease (TSD) is a congenital lysosomal storage disorder, caused by deficiency in the α-subunit of β-hexosaminidase A, leading to GM2 ganglioside accumulation in the central nervous system. Patients with TSD exhibit neural disturbances such as seizures, mental retardation; however, the molecular mechanisms behind neurological symptoms remain unclear. This study aimed to investigate altered synaptic function and explore treatment avenues for TSD. We observed the upregulation of postsynaptic receptors, abnormally elevated Ca2+ influx by neurotransmitter, and increased cell death under oxidative stress in TSD neurons. These abnormalities were associated with GM2 ganglioside accumulation. Additionally, we found that thiethylperazine, an approval drug for anti-emetics, mitigated GM2 ganglioside accumulation, potentially by activating the ATP-binding cassette subfamily C member 1 (ABCC1) transporter. This activation consequently improved the abnormal synaptic function. Our findings suggest that synaptic dysfunction is implicated in the neural disturbance in TSD, and highlight the ABCC1 transporter as a promising therapeutic target for this disease.
Τύπος εγγράφου: article
Περιγραφή αρχείου: electronic resource
Γλώσσα: English
ISSN: 1095-953X
Relation: http://www.sciencedirect.com/science/article/pii/S096999612500316X; https://doaj.org/toc/1095-953X
DOI: 10.1016/j.nbd.2025.107099
Σύνδεσμος πρόσβασης: https://doaj.org/article/d149617c31fa45df8bedacbdde1732b9
Αριθμός Καταχώρησης: edsdoj.149617c31fa45df8bedacbdde1732b9
Βάση Δεδομένων: Directory of Open Access Journals
Περιγραφή
ISSN:1095953X
DOI:10.1016/j.nbd.2025.107099