Details

Autor(en) / Beteiligte

• Zhang, Xiao-Fang
• Zhao, Yan-Feng
• Zhu, Shun-Wei
• Huang, Wei-Jie
• Luo, Yan
• Chen, Qing-Ying
• Ge, Li-Jun
• Li, Run-Sheng
• Wang, Jian-Fei
• Sun, Mu
• Xiao, Zhi-Cheng
• Fan, Guo-Huang

Titel

CXCL1 Triggers Caspase-3 Dependent Tau Cleavage in Long-Term Neuronal Cultures and in the Hippocampus of Aged Mice: Implications in Alzheimer's Disease

Ist Teil von

• Journal of Alzheimer's disease, 2015-01, Vol.48 (1), p.89-104

Ort / Verlag

Netherlands

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• Truncation of tau protein is considered an early event in Alzheimer's disease (AD) and is believed to play a major pathogenic role in sporadic AD. However, causative factors that trigger tau truncation in AD remain poorly understood. In the present study, we demonstrate that CXCL1 (C-X-C motif ligand 1), a specific ligand for the chemokine receptor CXCR2, induced cleavage of tau at ASP421 in a caspase-3-dependent manner in long-term but not short-term cultured neurons. The cleaved tau formed varicosities or bead-like structures along the neurites, an abnormal distribution of tau induced by CXCL1 that has not been observed previously. CXCL1-induced activation of GSK3β and the subsequent phosphorylation of tau preceded and were required for caspase-3 activation and tau cleavage. Moreover, intrahippocampal microinjection of lentiviral CXCL1 induced tau cleavage in hippocampal neurons in aged (15-18 months of age) but not adult mice (5-10 months of age). Our data highlight a new role of CXCR2 in tau cleavage and suggest that targeting CXCR2 may offer therapeutic benefits to patients with AD and potentially other tauopathies.