Modifications of apoptosis-related protein levels in lymphocytes of patients with Parkinson's disease. The effect of dopaminergic treatment

• Published in: Journal of Neural Transmission Vol. 111; no. 8; pp. 1017 - 1030
• Main Authors: Blandini, F, Cosentino, M, Mangiagalli, A, Marino, F, Samuele, A, Rasini, E, Fancellu, R, Tassorelli, C, Pacchetti, C, Martignoni, E, Riboldazzi, G, Calandrella, D, Lecchini, S, Frigo, G, Nappi, G
• Format: Journal Article
• Language: English
• Published: Austria Springer Nature B.V 01.08.2004
• Subjects: Aged; Antiparkinson Agents - therapeutic use; Apoptosis - drug effects; Apoptosis - physiology; Caspase 3; Caspases - metabolism; Cell Survival - drug effects; Disease Progression; Dopamine Agents - therapeutic use; Dopamine Agonists - pharmacology; Female; Humans; Levodopa - pharmacology; Lymphocytes - drug effects; Lymphocytes - enzymology; Lymphocytes - metabolism; Male; Middle Aged; Parkinson Disease - drug therapy; Parkinson Disease - metabolism; Peripheral Nervous System - drug effects; Peripheral Nervous System - metabolism; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Receptors, GABA-A - drug effects; Receptors, GABA-A - metabolism; Superoxide Dismutase - metabolism
• ISSN: 0300-9564; 1435-1463
• DOI: 10.1007/s00702-004-0123-1

In this study, we investigated whether changes in the regulatory mechanisms of apoptosis and oxidative stress may be detected, peripherally, in patients with Parkinson's disease (PD). For this purpose, we measured caspase-3 activity, Bcl-2 concentrations, peripheral benzodiazepine receptor (PBR) expression and Cu/Zn superoxide dismutase (SOD) concentrations in lymphocytes of untreated PD patients, patients treated only with L-Dopa or with L-Dopa and dopamine agonists and healthy volunteers. Caspase-3 activity was significantly increased in all PD patient groups. Patients treated with L-Dopa and dopamine agonists showed the lowest values of Bcl-2, coupled with the highest density of PBRs, while increased levels of Cu/Zn SOD were found in the group under monotherapy with L-Dopa. We also found, in PD patients, clear, negative correlations between Bcl-2 levels and both duration and severity of the disease. Our findings point to the existence of changes in the regulatory mechanisms of apoptosis in PD patients -- observable outside the central nervous system -- which seem to be modulated by the pharmacological treatment with dopaminergic agents.