γ-Secretase as a Therapeutic Target for Treatment of Alzheimers Disease

Title: γ-Secretase as a Therapeutic Target for Treatment of Alzheimers Disease

Volume: 12 Issue: 6

Author(s): Taisuke Tomita and Takeshi Iwatsubo

Affiliation:

Keywords: Alzheimer's disease, amyloid, γ-secretase, presenilin, aspartic protease, intramembrane proteolysis, protease inhibitor

Abstract: Alzheimers disease (AD) is the most common cause of dementia with aging, that is pathologically characterized by senile plaques that contain amyloid-b peptides (Aβ) and neurofibrillary tangles comprised of phosphorylated tau. Genetic and biological studies provide evidence that the production and deposition of Aβ contribute to the etiology of AD. g-Secretase is the pivotal enzyme in generating the C terminus of Aβ, that determines its aggregability and propensity for deposition. Drugs that regulate the production of Aβ by inhibiting g-secretase activity could provide an effective therapeutics for AD, although recent studies suggest that g-secretase plays important roles in novel signaling pathways that play essential roles in embryonic development. This review focuses on recent progresses in the g-secretase biology that shed substantial light on the proteolytic mechanism, regulation and composition of this unusual enzyme. Moreover, we review the recent development of inhibitors and provide a direction for the effective treatment of AD through inhibition of g-secretase activity.

Cite this article as:

Tomita Taisuke and Iwatsubo Takeshi, γ-Secretase as a Therapeutic Target for Treatment of Alzheimers Disease, Current Pharmaceutical Design 2006; 12 (6) . https://dx.doi.org/10.2174/138161206775474206