Affiliations: [a] Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Chuo-ku, Kumamoto, Japan
| [b] Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
Correspondence:
[*]
Correspondence to: Shokei Kim-Mitsuyama, MD, PhD, Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjyo, Chuo-ku, Kumamoto 860-8556, Japan. Tel.: +81 96 373 5082; Fax: +81 96 373 5082; E-mail: [email protected].
Abstract: To examine the role of ASK1 in Alzheimer’s disease (AD), we generated 5XFAD mice deficient in ASK1 and investigated the characteristics of old 5XFAD and wild-type mice with ASK1 deficiency. ASK1 deficiency improved cognitive function in 24-month-old 5XFAD mice, which was associated with the reduction of phosphorylated p38. Thus, ASK1/p38 cascade seems to play some role in the pathogenesis of AD in mice. In 24-month-old wild-type mice, ASK1 deficiency increased cerebral vasoreactivity to acetazolamide and significantly reduced brain soluble Aβ, which were also associated with the reduction of phosphorylated p38. Thus, ASK1/p38 cascade may contribute to brain aging of wild-type mice. Collectively, our present results provided the evidence suggesting the involvement of ASK1/p38 cascade in AD and brain aging.
