title: Long-term overexpression of heme oxygenase 1 promotes tau aggregation in mouse brain by inducing tau phosphorylation.
abstract: Intracellular tau aggregates composed of neurofibrillary tangles (NFTs) are a defining feature of Alzheimer's disease (AD). Increased expression of heme oxygenase-1 (HO-1) is a common phenomenon in AD. Interestingly, the spatial distribution of HO-1 expression is essentially identical to that of pathological accumulation of tau in AD. In this study, we developed a new transgenic mouse overexpressing HO-1, called CAG-HO-1 Tg mice, to explore the relationship between HO-1 and tau aggregation. In this model, we found that long-term overexpression of HO-1 significantly promoted tau aggregation in brain, by analyzing changes in morphology and insoluble tau expression levels. Moreover, our research provides the first in vivo evidence that HO-1 can enhance iron loading and tau (Ser199/202/396) phosphorylation in brains of transgenic mice. Cellular evidence indicates that HO-1 can induce the phosphorylation of tau through iron accumulation in Neuro2a cells stably transfected with HO-1. Our data suggest that long-term overexpression of HO-1 can promote tau aggregation. This mechanism involves excessive iron production mediated by HO-1 overexpression, which induces tau phosphorylation. Our results provide a potential pathway for the pathogenesis of tauopathies, which remains largely unknown.
authors: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors: Yang
authors: Y
authors: Hui
authors: Dayong
authors: D
authors: Wang
authors: Wenjing
authors: W
authors: Li
authors: Lina
authors: L
authors: Zhang
authors: Jianfeng
authors: J
authors: Jin
authors: Ning
authors: N
authors: Ma
authors: Lingyun
authors: L
authors: Zhou
authors: Osamu
authors: O
authors: Nakajima
authors: Weiming
authors: W
authors: Zhao
authors: Xu
authors: X
authors: Gao