Contribution of a metal-peroxide adduct to neurodegeneration is due to its oxidative protease activity.
Many hypotheses have been developed to explain aging and age-related neurodegenerative disorders; one of the most compelling is the role of oxidative stress to induce changes in protease activity in brains of patients of Alzheimer's disease and prion disease. At the moment however, there is no clear answer how protein degradation may be achieved in the brain. We have observed that several metal compounds can degrade proteins in the presence of hydrogen peroxide, and elucidated the reaction scheme based on the new theoretical point for the reactivity of a metal-peroxide adduct with eta 1-coordination mode. In this article we would like to point out the importance of a copper(II)-peroxide adduct to promote neurodegenerative diseases such as prion disease and amyotrophic lateral sclerosis through its oxidative protease function.
Nishida
Y
Y
Institute for Molecular Science, Okazaki, Japan. yuzo@ims.ac.jp
Nishino
S
S
D000375:Aging; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D001483:Base Sequence; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D008670:Metals / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009410:Nerve Degeneration / Q000201:enzymology / Q000378:metabolism*; D010545:Peroxides / Q000737:chemistry / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; D008670:Metals; D010545:Peroxides; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human