This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Alzheimer's Disease is characterized by the presence of senile plaques and neurofibrillary tangles in the brain accompanied by massive neuronal loss. The major component of the senile plaques is the A peptide, which is present in several isoforms from 39-42 amino acids long. The aggregation of this peptide is widely suspected (but far from proven) to be the cause of Alzheimer's disease. The A peptide is formed from the transmembrane domain of amyloid precursor protein, APP, and is one of the most hydrophobic natural peptides known which makes it particularly difficult to analyze. This peptide is cleaved from APP by a series of enzymes known as the secretases, and the steady state levels of the A-beta peptides in vivo are a direct result of the balance between their production and breakdown. The most described A degrading enzymes today are Neprilysin (NEP) and its family member ECE-insulin degrading enzyme (IDE) angiotensin converting enzyme (ACE) and Plasmin. We have previously demonstrated a strong A -degrading activity in serum-containing conditioned medium of human neuroblastoma cells. We recently identified the serine protease responsible for this activity to be acyl peptide hydrolase (APH, EC3.4.19.1). We confirmed the assignment of the protein's identity by MALDI-TOF MS and the degradation products of A were observed by gel electrophoresis.
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