biostudies-literatureSingh AKMinistry of Healthe13675https://www.ebi.ac.uk/biostudies/studies/S-EPMC9470894biostudies-literatureUnknown21(9)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 larAging cellGlucose 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.PMC9470894MOH‐000641‐00Pavon MVSajikumar SNeo SHLiwang CRao VJJoshi IVasudevan MSheila ARSinha SHSingh AKShetty MSLeng JCKEswaramoorthy MPang KKLNavakkode SKundu TKfalseGlucose 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.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 lar2022-01-01T00:00:00Z2022 Sep2026-06-20T03:25:27.45Z2025-04-04T20:19:39.542ZS-EPMC94708943596257610.1111/acel.13675