The effect of ATF6 deletion on ALS pathology

2016 Fiscal Year Final Research Report

• Project/Area Number: 26430069
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Kanazawa University
• Principal Investigator: Hori Osamu 金沢大学, 医学系, 教授 (60303947)
• Co-Investigator(Renkei-kenkyūsha): TAKARADA Mika 金沢大学, 医学系, 助教 (40565412)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 神経変性 / 小胞体ストレス

Outline of Final Research Achievements

To dissect the role of the unfolded protein response (UPR) in the pathology of amyotrophic lateral sclerosis (ALS), we crossed ALS (SOD G93A Tg) mice with Atf6α-/- mice, the latter of which lack ATF6a, a major sensor in the UPR. Analysis using ALS and ALS/Atf6α-/- mice revealed the onset time of ALS was significantly earlier in ALS/Atf6α-/- mice, but the life span was not significantly different between two genotypes. Consistent with these results, higher levels of SOD aggregation was observed in ALS/Atf6α-/- mice before the onset, while lower levels of activation was observed in Atf6α-/- mouse-derived microglia, compared with wild-type mouse-derived microglia. These results suggest the time- and cell type-specific regulation of ATF6 may play the important role in the pathology of ALS.

Free Research Field

神経解剖学