Translational Medicine
Open Access

Inhibition of Drp1 ameliorates Aβ deposition and restores synaptic depression and memory in Alzheimer’s disease model

4^th International Conference on Translational Medicine

October 26-28, 2015 Baltimore, USA

Dong-Gyu Jo1, Hak Kyun Kim1, Gun Young Jung1, Hee Jin Park1, Wook Kim2 and Jae Hyung Park1

1Sungkyunkwan University, Korea 2Ajou University, Korea

Posters-Accepted Abstracts: Transl Med

Abstract :

Mitochondrial dysfunction is an early and prominent feature of Alzheimerâ��s disease (AD). In brains of human AD cases as well as AD-like, A�² plaques are accumulated in mitochondria and may cause structural and functional abnormalities of mitochondria. In addition, mitochondrial abnormalities are found to arise before A�² plaque deposition. Mitochondria from AD brains show fractured cristae, reduced respiratory capacity and increased mitochondrial fragmentation. Both the treatment of A�² and the overexpression of A�² precursor protein (APP) highly induce synaptic injury in neuronal cells as well as massive mitochondrial fragmentation. Exposure to oligomeric A�² or excessive NO can lead to S-nitrosylation of Drp1 (SNO-Drp1) at Cys644 which activates Drp1 GTPase activity and results in the accumulation of excessively fragmented mitochondria. Moreover, Drp1 activity and the level of SNO-Drp1 were significantly elevated in the brains of sporadic AD cases. Therefore, the adjustment of imbalance of mitochondrial dynamics may have beneficial effects on mitochondrial structure, function and neuronal survival in AD. However, it remains to be determined whether inhibition of excessive mitochondrial fission is beneficial in mammal models of AD. In this study, we evaluated the effect of Drp1 inhibitor mdivi-1 on mitochondrial dysfunction and AD-like neuropathology in APP/PS1 double transgenic AD mice.

Biography :

Email: jodg@skku.edu