XBP1 and PERK Have Distinct Roles in Aβ-Induced Pathology

Kuan Chung Cheng, Hsueh Cheng Chiang

研究成果: Article同行評審

2 引文 斯高帕斯(Scopus)

摘要

Endoplasmic reticulum (ER) stress triggers multiple cellular signals to restore cellular function or induce proapoptosis that is altered in the brains of patients with Alzheimer’s disease (AD). However, the role of ER stress in β-amyloid (Aβ)-induced AD pathology remains elusive, and data obtained from different animal models and under different experimental conditions are sometimes controversial. The current study conducted in vivo genetic experiments to systematically examine the distinct role of each ER stress effector during disease progression. Our results indicated that inositol-requiring enzyme 1 was activated before protein kinase RNA-like endoplasmic reticulum kinase (PERK) activation in Aβ42 transgenic flies. Proteasome activity played a key role in this sequential activation. Furthermore, our study separated learning deficits from early degeneration in Aβ-induced impairment by demonstrating that X-box binding protein 1 overexpression at an early stage reversed Aβ-induced early death without affecting learning performance in the Aβ42 transgenic flies. PERK activation was determined to only enhance Aβ-induced learning deficits. Moreover, proteasome overactivation was determined to delay PERK activation and improve learning deficits. Altogether, the findings of this study demonstrate the complex roles of ER stress during Aβ pathogenesis and the possibility of using different ER stress effectors as reporters to indicate the status of disease progression.

原文English
頁(從 - 到)7523-7532
頁數10
期刊Molecular Neurobiology
55
發行號9
DOIs
出版狀態Published - 2018 九月 1

All Science Journal Classification (ASJC) codes

  • Neurology
  • Cellular and Molecular Neuroscience

指紋 深入研究「XBP1 and PERK Have Distinct Roles in Aβ-Induced Pathology」主題。共同形成了獨特的指紋。

引用此