Ryota Suzuki
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Ryota Suzuki has a total of 5 co-authors. Here are the top co-authors by number of shared publications:
- Chika Yoshida
Laboratory of Enzymology, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan
1 shared publication - Eugene Futai
Laboratory of Enzymology, Graduate School of Agricultural Sciences, Tohoku University, Sendai 980-8572, Japan
1 shared publication - Haruka Takahashi
Laboratory of Enzymology, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan
1 shared publication - Masafumi Hidaka
Department of Agricultural Chemistry, Graduate School of Agricultural Science, Tohoku University
1 shared publication - Tomohisa Ogawa
Department of Agricultural Chemistry, Graduate School of Agricultural Science, Tohoku University
1 shared publication
Latest Publications
- Open Access
- 16 February 2023
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 24 (4) , 3970
Specific Mutations near the Amyloid Precursor Protein Cleavage Site Increase γ-Secretase Sensitivity and Modulate Amyloid-β Production
Amyloid-β peptides (Aβs) are produced via cleavage of the transmembrane region of the amyloid precursor protein (APP) by γ-secretase and are responsible for Alzheimer’s disease. Familial Alzheimer’s disease (FAD) is associated with APP mutations that disrupt the cleavage reaction and increase the production of neurotoxic Aβs, i.e., Aβ42 and Aβ43. Study of the mutations that activate and restore the cleavage of FAD mutants is necessary to understand the mechanism of Aβ production. In this study, using a yeast reconstruction system, we revealed that one of the APP FAD mutations, T714I, severely reduced the cleavage, and identified secondary APP mutations that restored the cleavage of APP T714I. Some mutants were able to modulate Aβ production by changing the proportions of Aβ species when introduced into mammalian cells. Secondary mutations include proline and aspartate residues; proline mutations are thought to act through helical structural destabilization, while aspartate mutations are thought to promote interactions in the substrate binding pocket. Our results elucidate the APP cleavage mechanism and could facilitate drug discovery.
- 16 February 2023
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 24 (4) , 3970
Open AccessSpecific Mutations near the Amyloid Precursor Protein Cleavage Site Increase γ-Secretase Sensitivity and Modulate Amyloid-β Production
Amyloid-β peptides (Aβs) are produced via cleavage of the transmembrane region of the amyloid precursor protein (APP) by γ-secretase and are responsible for Alzheimer’s disease. Familial Alzheimer’s disease (FAD) is associated with APP mutations that disrupt the cleavage reaction and increase the production of neurotoxic Aβs, i.e., Aβ42 and Aβ43. Study of the mutations that activate and restore the cleavage of FAD mutants is necessary to understand the mechanism of Aβ production. In this study, using a yeast reconstruction system, we revealed that one of the APP FAD mutations, T714I, severely reduced the cleavage, and identified secondary APP mutations that restored the cleavage of APP T714I. Some mutants were able to modulate Aβ production by changing the proportions of Aβ species when introduced into mammalian cells. Secondary mutations include proline and aspartate residues; proline mutations are thought to act through helical structural destabilization, while aspartate mutations are thought to promote interactions in the substrate binding pocket. Our results elucidate the APP cleavage mechanism and could facilitate drug discovery.