TTK21

TTK21 is an activator of the histone acetyltransferases CBP/p300. TTK21 passes the blood–brain barrier, induces no toxicity, and reaches different parts of the brain when conjugated to glucose-based carbon nanosphere (CSP). TTK21 has beneficial implications for the brain functions of neurogenesis and long-term memory^[1].CSP-TTK21 can ameliorate Aβ-impaired long-term potentiation (LTP). CSP-TTK21 may enhance the transcription of genes that promote synaptic health and cognitive function^[2]. CSP-TTK21 is orally effective and leads to improvements in motor functions, histone acetylation dynamics in a spinal injury rat model^[3]. In Vitro:TTK21 (50-275 μM) is able to concentration-dependently activate CBP and p300 acetyltransferases and increase histone acetylation. Effectively activates CBP/p300 activity and increases the acetylation of histone H3 and H4. 100 μM TTK21 can promote the self-acetylation of p300^[1].
TTK21 (50-275 μM; 6-24 h) in Hela cells, can't effectively penetrate the cell membrane to enter the cell by itself. However, when combined with carbon nanosphere CSP, it is able to enter SH-SY5Y neuronal cells and significantly increase the acetylation level of histone H3, indicating that the CSP-TTK21 complex has the ability to penetrate the cell membrane^[1].
CSP-TTK21 (0.36 µg/ml; 1 h) can restor protein synthesis-dependent long-term potentiation (LTP) damage caused by Aβ (1-42) multimerst^[2].
In Vivo:CSP-TTK21 ((TTK21 conjugated to carbon nanosphere, CSP-TTK21) 20 mg/kg; i.p.; single dose) can extend the memory duration^[1].
CSP-TTK21 (20 mg/kg; p.o; single dose) enhances long-term potentiation comparably to intraperitoneal injection, suggesting effective memory enhancement in Wild-type mice^[3].
CSP-TTK21 (10 mg/kg; p.o; weekly) promotes motor recovery after spinal cord injury in rats, and enhances the expression of regeneration-associated genes in the prefrontal cortex and cerebellum following spinal cord injury^[3].