title: Peripheral proteasome and caspase activity in Parkinson disease and Alzheimer disease.
abstract: BACKGROUND
  Defects of the ubiquitin-proteasome (UP) system, a multicatalytic complex degrading polyubiquitinated proteins, may intervene in the pathogenesis of neurodegenerative disorders characterized by intracellular formation of protein aggregates such as Parkinson disease (PD) and Alzheimer disease (AD) by inducing proapoptotic conditions.
  
  
  METHODS
  The authors measured the activity of proteolytic UP core, proteasome 20S, and of proapoptotic caspase-3 and -9 in peripheral blood lymphocytes (PBLs) of PD and AD patients to establish whether changes in these systems are detectable peripherally.
  
  
  RESULTS
  Proteasome 20S activity was reduced in PBLs of treated PD patients vs healthy controls (mean +/- SEM: 1.0 +/- 0.1 vs 2.3 +/- 0.2 nmol 7-amino-4-methylcoumarin (AMC)/10(6) cells, p < 0.001), whereas marked increases in caspase-3 activity (1370 +/- 153 vs 586 +/- 104 pmol AMC/10(6) cells, p < 0.001) and caspase-9 activity (873 +/- 86 vs 304 +/- 27 U/10(6) cells, p < 0.001) were found. Increased caspase-9 activity was also detected in PBLs of untreated PD patients (900 +/- 193 U/10(6) cells). PD duration and severity (Unified Parkinson's Disease Rating Scale score) were inversely correlated with proteasome 20S activity and directly correlated with caspase-3 activity. An inverse correlation was also observed in PD patients between caspase-3 activity and proteasome 20S activity. No significant changes in proteasome 20S or caspase activity or correlations between biochemical and clinical variables were found in patients with AD.
  
  
  CONCLUSIONS
  A decrease in proteasome activity, possibly related to caspase activation, is detectable in peripheral blood lymphocytes of patients with Parkinson disease but not patients with Alzheimer disease, suggesting that these variables may be considered for the development of peripheral biomarkers of Parkinson disease.
authors.affiliation: Laboratory of Functional Neurochemistry, IRCCS Neurological Institute C. Mondino, Pavia, Italy. fabio.blandini@mondino.it
authors.forename: F
authors.initials: F
authors.lastname: Blandini
authors.forename: E
authors.initials: E
authors.lastname: Sinforiani
authors.forename: C
authors.initials: C
authors.lastname: Pacchetti
authors.forename: A
authors.initials: A
authors.lastname: Samuele
authors.forename: E
authors.initials: E
authors.lastname: Bazzini
authors.forename: R
authors.initials: R
authors.lastname: Zangaglia
authors.forename: G
authors.initials: G
authors.lastname: Nappi
authors.forename: E
authors.initials: E
authors.lastname: Martignoni
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000201:enzymology; D000978:Antiparkinson Agents / Q000627:therapeutic use; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000097:blood*; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood* / Q000188:drug therapy / Q000201:enzymology; D046988:Proteasome Endopeptidase Complex / Q000097:blood*; D012016:Reference Values
chemical_list: D000978:Antiparkinson Agents; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; D046988:Proteasome Endopeptidase Complex