In:
The EMBO Journal, EMBO, Vol. 42, No. 4 ( 2023-02-15)
Abstract:
image The synapto‐nuclear shuttling protein Jacob assembles and docks a signalosome to the transcriptional regulator CREB to promote CREB de‐phosphorylation and neuronal cell death. Here, β‐amyloid peptide (Aβ) is found to cause Alzheimer‐associated synapse loss by regulating nuclear translocation of Jacob, providing a potential target for therapeutic intervention. Aβ promotes nuclear translocation of Jacob in Alzheimer's disease (AD) patient brains and mouse hippocampal neurons. Aβ‐regulated trafficking of Jacob induces transcriptional inactivation of cAMP‐responsive element‐binding protein (CREB), leading to synapse impairment and loss in an AD mouse model. The small‐molecular compound Nitarsone selectively prevents the assembly of the Jacob/LMO4/PP1 signalosome to promote CREB transcriptional activity. Nitarsone prevents synaptic plasticity impairment and cognitive decline in mouse models of AD.
Type of Medium:
Online Resource
ISSN:
0261-4189
,
1460-2075
DOI:
10.15252/embj.2022112453
Language:
English
Publisher:
EMBO
Publication Date:
2023
detail.hit.zdb_id:
1467419-1
detail.hit.zdb_id:
586044-1
SSG:
12
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