The Increase of D-Amino Acids in Alzheimer′s Disease-Related Proteins Isolated from the Brains of SAMP8 Mice

Abstract

Recently, the presence and function of D-amino acids in mammals, including humans, have been reported. In particular, a relationship between an increase in the D-amino acid content of specific proteins and aging and senescence-related diseases has been proposed. However, this hypothesis remains unproven. Here, we focused on Alzheimer′s disease, a well known senescence-related disease, and used high performance liquid chromatography (HPLC) to analyze the degree of change in the D-amino acid content in the Alzheimer′s disease−elated proteins PP1C, GLRX1 and NF-L. Cerebrums of SAM (senescence-accelerated mice), an animal model of Alzheimer′s disease, were used. Increases in D-serine and D-aspartic acid contents with aging in PP1C were found. PP1C is a catalytic subunit of PP1 (serine/threonine phosphatase 1). Tau, one of the most important molecules involved in Alzheimer′s disease, is a target of PP1C. Hyperphosphorylation of Tau is thought to be a trigger of Alzheimer′s disease. Moreover, the involvement of PP1C in cognitive function and memory, independently of dephosphorylation of Tau, has been suggested. The results of this study suggest that substitution of L-amino acids with D-amino acids alters the physical properties of PP1C, and this, in turn, causes its malfunction, which may lead to the onset of Alzheimer′s disease.