Identification of Putative Amyloid A4-Splitting Enzymes with Two Endopeptidases Widely Distributed in Mammalian Cells
Alzheimer’s disease (AD) is characterized by the deposition of amyloid in the brain, especially in senile plaques and neurofibrillary tangles. Amyloid is thought to arise by abnormal cleavage of various proteins into self-aggregating fragments. The major component of AD amyloid is a 4.2-kD polypeptide referred to as the A4 or β-protein, and it corresponds to a membrane-spanning domain of a putative amyloid precursor protein (APP). A4 at positions 597 to 638 of the initially identified APP695 is hydrophobic and the C-terminal half of the A4 is buried in the membrane. The major peptide species in the amyloid plaque core in AD are peptide A4′, which corresponds to Phe600 to Ala638, and an A4 peptide.
KeywordsNeurofibrillary Tangle Prolyl Endopeptidase Abnormal Cleavage Multicatalytic Proteinase Porcine Skeletal Muscle
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