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- Title
アミロイドβ に対する凝集抑制・乖離促進作用を有する 短鎖ペプチドのアルツハイマー病治療薬としての可能性
- Authors
東 洋一郎
- Abstract
Lecanemab is a new anti-amyloid antibody being developed as a treatment for Alzheimer's disease. It is expected to delay the progression of the disease by reducing the accumulation of amyloid beta (Aβ) in the brain. However, no drug has been developed that can completely eliminate Aβ and improve symptoms. A representative Catalytide, JAL-TA9 (YKGSGFRMI), cleaves Aβ42 and improves symptoms in an Alzheimer's disease mouse model, suggesting that JAL-TA9 is a promising candidate for treating Alzheimer's disease by effectively eliminating Aβ. The catalytic center of JAL-TA9 is GSGFR. To identify better Catalytides for Alzheimer's treatment, we analyzed the structure-activity relationship of 21 point-mutated GSGFR derivatives. In this process, we discovered two peptides, GSGFK and GSGNR, that not only inhibit Aβ25-35 aggregation but also dissolve aggregated Aβ25-35. Intracerebroventricular administration of GSGFK protected mice against Aβ25-35-induced short-term memory deficits and promoted microglial phagocytic activity. Like Lecanemab, GSGFK targets Aβ, but it has advantages such as safety, administration method, and cost. In this talk, we will discuss the potential of GSGFK as a therapeutic candidate for Alzheimer's disease.
- Subjects
ALZHEIMER'S disease; DISEASE progression; SHORT-term memory; MEMORY disorders; STRUCTURE-activity relationships
- Publication
Folia Pharmacologica Japonica, 2024, Vol 159, Issue 6, p402
- ISSN
0015-5691
- Publication type
Academic Journal
- DOI
10.1254/fpj.24077