In:
Aging Cell, Wiley, Vol. 21, No. 9 ( 2022-09)
Abstract:
The master epigenetic regulator lysine acetyltransferase (KAT) p300/CBP plays a pivotal role in neuroplasticity and cognitive functions. Recent evidence has shown that in several neurodegenerative diseases, including Alzheimer's disease (AD), the expression level and function of p300/CBP are severely compromised, leading to altered gene expression causing pathological conditions. Here, we show that p300/CBP activation by a small‐molecule TTK21, conjugated to carbon nanosphere (CSP) ameliorates Aβ‐impaired long‐term potentiation (LTP) induced by high‐frequency stimulation, theta burst stimulation, and synaptic tagging/capture (STC). This functional rescue was correlated with CSP‐TTK21‐induced changes in transcription and translation. Mechanistically, we observed that the expression of a large number of synaptic plasticity‐ and memory‐related genes was rescued, presumably by the restoration of p300/CBP mediated acetylation. Collectively, these results suggest that small‐molecule activators of p300/CBP could be a potential therapeutic molecule for neurodegenerative diseases like AD.
Type of Medium:
Online Resource
ISSN:
1474-9718
,
1474-9726
Language:
English
Publisher:
Wiley
Publication Date:
2022
detail.hit.zdb_id:
2099130-7
SSG:
12
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