In:
Science Translational Medicine, American Association for the Advancement of Science (AAAS), Vol. 15, No. 698 ( 2023-05-31)
Abstract:
Pathogenic proteasome gene variants are associated with a broad spectrum of diseases. Ebstein and colleagues identified 15 de novo missense variants in the PSMC3 proteasome gene in patients with neurodevelopmental delay. Expression of PSMC3 variants in mouse neuronal cultures led to altered dendrite development, and deletion of the fly PSMC3 ortholog resulted in learning deficits in the fruit flies. Proteasome dysfunction in T cells from patients with PSMC3 variants led to upregulation of proteotoxic markers and production of interferon type I that could be alleviated by inhibition of protein kinase R. These findings implicate PSMC3 pathogenic variants in neurodevelopmental disorders and suggest a therapeutic strategy for patients carrying these missense mutations. —Daniela Neuhofer
Type of Medium:
Online Resource
ISSN:
1946-6234
,
1946-6242
DOI:
10.1126/scitranslmed.abo3189
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2023