title: Clearance of genetic variants of amyloid β peptide by neuronal and non-neuronal cells.
abstract: The presence of senile plaques in the brain is one of the pathological hallmarks of Alzheimer's disease (AD). The biogenesis and clearance of the amyloid β peptide (A β ), the main component of the lesions, lie at the center of the pathogenesis of AD. In sporadic AD, the increase of A β levels seems to be indicative of failure of clearance mechanisms. We previously showed that the clearance of the wild type A β40 peptide by various neuronal and non-neuronal cells occurs through a same proteolytic process and that A β degradation was primarily dictated by its conformational state (Panchal et al., 2007). To gain further insights on the role of the peptide conformation in the clearance mechanism of A β , two A β40 peptides, known to be associated with amyloid angiopathy (Dutch and Flemish mutations), and the rodent A β40 peptide were catabolized by several cells by using the same experimental approach. The peptide fragments, generated by proteolytic cleavage of substrates in cell supernatants, were identified by LC-MS and the cleavage sites of proteases were deduced. In parallel, conformational states of wild type A β 40 peptide and of the three A β 40 variants were characterized by circular dichroism spectroscopy. We provide data suggesting that discrete conformational changes of A β 40 peptide regulate its clearance rate by neuronal and non-neuronal cells.
authors.affiliation: Laboratoire de Biochimie des Signaux Régulateurs Cellulaires et Moléculaires, FRE 2621 CNRS, Université Pierre et Marie Curie (Paris 6), Paris, France.
authors.forename: Maï
authors.initials: M
authors.lastname: Panchal
authors.forename: Boutaïna
authors.initials: B
authors.lastname: El Abida
authors.forename: Noureddine
authors.initials: N
authors.lastname: Lazar
authors.forename: Christine
authors.initials: C
authors.lastname: Fahy
authors.forename: Lionel
authors.initials: L
authors.lastname: Dubost
authors.forename: Bertrand
authors.initials: B
authors.lastname: Friguet
authors.forename: Mohamed
authors.initials: M
authors.lastname: Rholam
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002522:Chlorocebus aethiops; D002942:Circular Dichroism; D006224:Cricetinae; D003412:Cricetulus; D017077:Culture Media, Conditioned; D006801:Humans; D020014:K562 Cells; D007700:Kinetics; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000737:chemistry* / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D051381:Rats; D016415:Sequence Alignment
chemical_list: D016229:Amyloid beta-Peptides; D017077:Culture Media, Conditioned; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)