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Glucose derived carbon nanosphere (CSP) conjugated TTK21, an activator of the histone acetyltransferases CBP/p300, ameliorates amyloid-beta 1-42 induced deficits in plasticity and associativity in hippocampal CA1 pyramidal neurons

Authors :
Akash K. Singh
Sin H. Neo
Christine Liwang
Karen K. L. Pang
Jason C. K. Leng
Sarmistha H. Sinha
Mahesh S. Shetty
Madavan Vasudevan
Vinay J. Rao
Ila Joshi
Muthusamy Eswaramoorthy
Maria V. Pavon
Ang R. Sheila
Sheeja Navakkode
Tapas K. Kundu
Sreedharan Sajikumar
Source :
Aging cell. 21(9)
Publication Year :
2022

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.

Details

ISSN :
14749726
Volume :
21
Issue :
9
Database :
OpenAIRE
Journal :
Aging cell
Accession number :
edsair.doi.dedup.....a8193b92fe891342ec5db86fa0bd2eb6