title: Prolyl oligopeptidase colocalizes with α-synuclein, β-amyloid, tau protein and astroglia in the post-mortem brain samples with Parkinson's and Alzheimer's diseases.
abstract: Prolyl oligopeptidase (EC 3.4.21.26, PREP) is a serine protease that hydrolyzes proline-containing peptides shorter than 30-mer but it has also nonhydrolytic functions. PREP has been shown to accelerate aggregation of wild-type α-synuclein (α-syn) under cell-free conditions, and PREP inhibitors can block this aggregation both in vitro and in vivo. α-syn is the main component of Lewy bodies in Parkinson's disease (PD) and Lewy body dementia. To clarify the possible interaction of PREP with other markers of neurodegenerative diseases, we studied colocalizations of PREP and (1) α-syn, (2) β-amyloid, (3) tau protein and (4) astroglial and microglial cells in human post-mortem brain samples from PD, Alzheimer's disease (AD) patients and in healthy control brain samples. In the substantia nigra of PD brains, an intense colocalization with PREP and α-syn was evident. PREP colocalized also with β-amyloid plaques in AD brains and with tau protein in AD and in healthy brains. PREP was also found in astroglial cells in PD, AD and control brains, but not in the microglia. Our findings are the first ones to demonstrate colocalization of PREP and pathological proteins in the human brain and support the view that, at least in spatial terms, PREP could be associated with pathogenesis of neurodegenerative diseases.
authors.affiliation: Division of Pharmacology and Toxicology, Viikinkaari 5E (P.O. Box 56), FI-00014 University of Helsinki, Finland. Mirva.Hannula@helsinki.fi
authors.forename: M J
authors.initials: MJ
authors.lastname: Hannula
authors.forename: T T
authors.initials: TT
authors.lastname: Myöhänen
authors.forename: J
authors.initials: J
authors.lastname: Tenorio-Laranga
authors.forename: P T
authors.initials: PT
authors.lastname: Männistö
authors.forename: J A
authors.initials: JA
authors.lastname: Garcia-Horsman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D017628:Microglia / Q000378:metabolism; D008875:Middle Aged; D010300:Parkinson Disease / Q000378:metabolism*; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D051844:alpha-Synuclein; D016875:tau Proteins; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases