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NEUROLOGY 2006;66:529-534
© 2006 American Academy of Neurology

Peripheral proteasome and caspase activity in Parkinson disease and Alzheimer disease

F. Blandini, MD, E. Sinforiani, MD, C. Pacchetti, MD, A. Samuele, PhD, E. Bazzini, PhD, R. Zangaglia, MD, G. Nappi, MD and E. Martignoni, MD

From the Laboratory of Functional Neurochemistry (F.B., A.S., E.B., G.N.), Alzheimer Disease Assessment Unit and Laboratory of Neuropsychology (E.S.), Center for Parkinson’s Disease and Movement Disorders (C.P., R.Z.), IRCCS Neurological Institute "C. Mondino," Pavia; IRCCS "S. Maugeri" Foundation (E.M.), Scientific Institute of Veruno, Veruno; A. Avogadro University of Eastern Piedmont (E.M.), Novara; and Department of Neurology and Otorhinolaryngology (G.N.), University of Rome "La Sapienza," Rome, Italy.

Address correspondence and reprint requests to Dr. Fabio Blandini, Laboratory of Functional Neurochemistry, IRCCS Neurological Institute "C. Mondino," Via Mondino 2, 27100 Pavia, Italy; e-mail: fabio.blandini{at}mondino.it

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)/106 cells, p < 0.001), whereas marked increases in caspase-3 activity (1370 ± 153 vs 586 ± 104 pmol AMC/106 cells, p < 0.001) and caspase-9 activity (873 ± 86 vs 304 ± 27 U/106 cells, p < 0.001) were found. Increased caspase-9 activity was also detected in PBLs of untreated PD patients (900 ± 193 U/106 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.

This work was supported by grants of the Italian Ministry of Health to the IRCCS Neurologic Institute "C. Mondino" (Ricerca Corrente 2003; Ricerca Finalizzata 2003).

Disclosure: The authors report no conflicts of interest.

Received July 20, 2005. Accepted in final form October 26, 2005.




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