Laboratory for Proteolytic Neuroscience
Laboratory Head
Takaomi SAIDO (Ph.D.)
The aim of our research is to understand the mechanism of brain aging with specific emphasis on the study Alzheimer's disease (AD) through proteolysis. Proteolytic reactions often play critical roles in both physiological and pathological circumstances because of their irreversible nature, but their actual in vivo functions particularly in brain are not yet well understood. Among the various aspects of protease involvement in neuropathophysiology, our research focuses on two major themes. One is the metabolism of amyloid-βpeptide (Aβ), the cortical deposition of which triggers the pathological cascade leading to AD. Under physiological conditions, Aβ is constantly produced from its precursor and immediately catabolized, whereas dysmetabolism of Aβ seems to lead to pathological deposition upon aging. By elucidating the mechanism of Aβ metabolism, we intend to establish a new approach to prevent AD development by reducing Aβ burdens in aging brains. We also began to establish a novel amyloid imaging approach using a high-power microMRI. The other objective of our research is to define the roles of intracellular proteases, calpains and caspases, in the processes of neuronal dysfunction and degeneration in AD and other neurodegenerative diseases. Because these processes are relatively downstream to Aβ deposition in the disease cascade, we expect the outcome to contribute to AD research in therapeutic rather than preventive terms.
- Analysis of Abeta-degrading mechanism in brain
- Animal models for human brain aging
- The role of cellular proteases in aging-associated pathological changes
- Saito, T., Suemoto, T., Brouwers, N., Sleegers, K., Funamoto, S., Mihira, M., Matsuba, Y., Yamada, K., Nilsson, P., Takano, J., Nishimura, M., Iwata, N., Van Broeckhoven, C., Ihara, Y., Saido, T.C.
" Potent amyloidogenicity and pathogenicity of Aβ43."
Nat. Neurosci.,14, 1023-1032 (2011). - Takano, J., Mihira, N., Fujioka, R., Hosoki, E., Chishti, A.H., Saido, T.C.
" Vital role of the calpain-calpastatin system for placental integrity-dependent embryonic survival."
Mol. Cell Biol., 31, 4097-4106 (2011). - Higuchi, M., Iwata, N., Matsuba, Y., Takano, J., Suemoto, T., Maeda, J., Ji, B., Ono, M., Staufenbiel, M., Suhara, T., Saido, T.C.
" Mechanistic involvement of the calpain-calpastatin system in Alzheimer neuropathology."
FASEB J., in press. - Nilsson, P., Iwata, N., Muramatsu, S-I., Tjernberg, L.O., Winblad, B., Saido T.C.
" Gene therapy in Alzheimer's disease -potential for disease modification."
J. Cell Mol. Med.14, 714-757(2010) - Huang, S.M., Mouri, A., Kokubo, H., Nakajima, R., Suemoto, T., Higuchi, M., Staufenbiel, M., Noda, Y., Yamagushi, H., Nabeshima, T., Saido, T.C., Iwata, N.
" Neprilysin-sensitive synapse-associated amyloid b peptide oligomers impair neurornal plasticity and cognitive function."
J. Biol. Chem.,281, 17941-17951(2006). - Higuchi, M., Iwata, N., Matsuba, Y., Sato, K., Sasamoto, K., and Saido, T.C.
" 19F- and 1H-MRI detection of amyloid-βpeptide in vivo."
Nature Neurosci., 8, 527-533 (2005). - Saito, T., Iwata, N., Tsubuki, S., Takaki, Y., Takano, J., Huang, S.-H., Suemoto, T., Higuchi, M., and Saido, T.C.
" Somatostatin regulates brain amyloid β peptide, Aβ42, through modulation of proteolytic degradation."
Nature Med., 11, 434-439 (2005). - Tsubuki, S., Takaki, Y., and Saido, T.C.:
" Dutch, Flemish, Italian, and Arctic mutations of APP and resistance of Aβ to physiologically relevant proteolytic degradation."
Lancet, 361, 1957-1958 (2003). - Iwata, N., Tsubuki, S., Takaki, Y., Shirotani, K., Lu, B., Gerard, N.P., Gerard, C., Hama, E., Lee, H.-J., and Saido, T. C.
" Metabolic regulation of brain Aβ by neprilysin."
Science, 292, 1550-1552 (2001). - Iwata, N., Tsubuki, S., Takaki, Y., Watanabe, K., Sekiguchi, M., Hosoki, E., Kawashima-Morishima, M., Lee, H.-J., Hama, E., Sekine-Aizawa, Y., and Saido, T. C.
" Identification of the major Aβ1-42-degrading catabolic pathway in brain parenchyma: Suppression leads to biochemical and pathological deposition"
Nature Med., 6, 143-151 (2000).
Principal Investigator
- Takaomi SAIDO
- Laboratory Head
Members
- Takashi SAITO
- Deputy Laboratory Head
- Jiro TAKANO
- Research Scientist
- Per NILSSON
- Research Scientist
- Ko SATO
- Research Scientist
- Naomasa KAKIYA
- Research Scientist
- Hayato ISSHIKI
- Research Scientist
- Shoko HASHIMOTO
- Research Scientist
- Satoshi TSUBUKI
- Research Specialist
- Kenichi NAGATA
- Visiting Researcher
- Yukio MATSUBA
- Technical Staff I
- Ryo FUJIOKA
- Technical Staff I
- Misaki SEKIMOTO
- Technical Staff I
- Emi TAKANO
- Technical Staff I
- Yukiko WATANABE
- Technical Staff I
- Naomi MIHIRA
- Technical Staff II
- Masaki NISHIMURA
- Visiting Scientist
- Makoto HIGUCHI
- Visiting Scientist
- Tadashi MIYATAKE
- Visiting Scientist
- Masashi ASAI
- Visiting Scientist
- Masaki IMAGAWA
- Visiting Scientist
- Masayuki YOKOTA
- Visiting Scientist
- Akiko ETO
- Visiting Scientist
- Hiroyuki ARAI
- Visiting Scientist
- Masahiro MARUYAMA
- Visiting Scientist
- Kyoko OHNO
- Visiting Scientist
- Nobuhisa IWATA
- Visiting Scientist
- Kei MARUYAMA
- Visiting Scientist
- Kaori IWATA
- Visiting Technician
- Mieko FUJITA
- Part-time Staff