dual-function stress response protein

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462921
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Nagasaki University
• Principal Investigator: HOTOKEZAKA Yuka 長崎大学, 病院(歯学系), 講師 (10244089)
• Co-Investigator(Kenkyū-buntansha): KATAYAMA Ikuo 長崎大学, 医歯薬学総合研究科(歯学系), 助教 (80295089) ; TASHIRO Shigeki 長崎大学, 病院(医学系), 助教 (20300882) ; EIDA Sato 長崎大学, 医歯薬学総合研究科(歯学系), 助教 (80325662) ; NAKAMURA Takashi 長崎大学, 医歯薬学総合研究科(歯学系), 教授 (30172406)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: γ-taxilin / αNAC / ER stress / Alzheimer’s diseases / hypoxia

Outline of Final Research Achievements

The signaling pathway leading to the endoplasmic reticulum (ER) stress responses has not been fully elucidated. Here we showed that glycogen synthase kinase-3β (GSK-3β)-dependent downregulation of γ-taxilin and nascent polypeptide-associated complex α-subunit (αNAC) mediates hypoxia-induced unfolded protein responses (UPRs) and the subsequent apoptotic pathways. However, the ER stress signaling pathways initiated by γ-taxilin or αNAC were distinct, triggering different ER stress sensors and activating different downstream pathways. γ-taxilin ablation induced tau hyperphosphorylation alone. Notably, downregulation of γ-taxilin and αNAC occurs in the brain of patients with Alzheimer’s disease. These results suggest that γ-taxilin and αNAC merge to regulate hypoxia-induced ER stress responses and provide a new insight into the pathogenesis of Alzheimer’s diseases.

Free Research Field

歯学・病態科学系歯学・歯科放射線学