12:00- 13:00 Nobuhisa Iwata (Nagasaki University)
Cutting edge Seminar
Speaker: Nobuhisa Iwata (Professor, Department of Genome-based Drug Discovery Graduate School of Biomedical Sciences Nagasaki University)
Title: A disease mechanism-based therapy for Alzheimer’s disease
Date&Time: 7 Sep. (Wed.) 2016, 12:00- 13:00
Venue: Conference Room(1F), IMEG
Abstract.
Aggregation and deposition of amyloid-β peptide (Aβ) in the brain are triggering events of the long-term pathological cascade of Alzheimer’s disease (AD), and are closely associated with the metabolic balance between Aβ anabolic and catabolic activities. As almost all familial AD mutations cause an increase in the anabolism of a particular form of Aβ, Aβ1-42, leading to Aβ deposition and accelerating AD pathology, a chronic reduction in the catabolic activity would also promote Aβ deposition. Neprilysin is a rate-limiting peptidase involved in brain Aβ catabolism. Mounting evidence that expression levels of neprilysin are decreased in the hippocampus and cerebral cortex of AD patients from the early stages of disease development and also with aging in humans, suggests a close association of neprilysin with the etiology and pathogenesis of AD. Thus, a subtle but long-term decline in neprilysin activity appears to be at least partly responsible for the memory-related symptoms of AD, and up-regulation of neprilysin would be a promising strategy for disease-modifying therapy of AD. In this lecture, I will talk about several approaches to up-regulate neuronal neprilysin activity in the brain.
References:
1) Iwata N. et al., Nat. Med., 6, 143-150 (2000).
2) Iwata N. et al., Science, 292, 1550-1552 (2001).
3) Iwata N. et al., Pharmacol. Ther., 108, 129-148 (2001).
4) Saito T. et al., Nat. Med., 11, 434-439 (2005).
5) Iwata N. et al., Sci. Rep., 3, 1472 (2013).
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