Review Article
New Insight into Alzheimer's Disease via Caspase 3-cleaved Tau: Pathogenic Role in Tau Oligomer Formation and Memory Deficits
Young Doo Kima, Jisu Parka and Yong Keun Jung*Global Research Laboratory, School of Biological Sciences, Seoul National University, Seoul 151-747, Korea
- Corresponding Author:
- Youn Keun Jung
School of Biological Sciences
Seoul National University, 1 Gwanak-ro
Gwanak-gu, Seoul 151-747, Korea
Tel: 8228804401
E-mail: ykjung@snu.ac.kr
Received date: June 21, 2017; Accepted date: June 28, 2017; Published date: July 05, 2017
Citation: Kima YD, Parka J, Jung YK (2017) New Insight into Alzheimer’s Disease via Caspase 3-cleaved Tau: Pathogenic Role in Tau Oligomer Formation and Memory Deficits. J Alzheimers Dis Parkinsonism 7:344. doi:10.4172/2161-0460.1000344
Copyright: © 2017 Kima YD, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Alzheimer’s disease (AD) is the most common and leading cause of dementia. AD has two different pathological hallmarks, extracellular amyloid beta plaques and intracellular neurofibrillary tangles (NFT). NFTs consist of abnormally modified tau protein that forms protein aggregates. Tau protein aggregates are prevalently observed as disease progresses and are believed to cause neuronal dysfunction. The caspase-3 cleaved form of tau, TauC3, is generated in cultured neurons under stress and is found in the brains of patients with AD in the early stages of disease when patients are asymptomatic. TauC3 accelerates tau oligomerization in vitro and in vivo, and induces neuronal degeneration. Moreover, the neuronal expression of TauC3 in transgenic mice causes memory deficits at a young age, which is concomitant with the appearance of tau oligomers. The removal of TauC3-containing oligomers and aggregates using drug treatment improves both memory and synaptic function. These findings demonstrate that TauC3 is critical for the formation of tau oligomers and small aggregates and may ultimately play a role in the rapid memory impairments observed in AD. Overall, TauC3 may represent a new therapeutic target for the prevention of AD.
