Apoptosis of peripheral blood lymphocytes in patients with LRRK2-assoctated Parkinson's disease

Mutations in the Leucine Reach Repeat Kinase 2 (LRRK2) gene are the most frequent cause of familial Parkinson's disease (PD). Although the precise physiological and pathological role of LRRK2 is unclear, a direct link between mutant LRRK2 and apoptosis has been suggested. Using flow cytometric...

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Bibliographic Details
Published inT͡S︡itologii͡a Vol. 54; no. 1; p. 44
Main Authors Usenko, T S, Emel'ianov, A K, Iakimovskiĭ, A F, Bogan'kova, N A, Vavilova, T V, Shvartsman, A L, Pchelina, S N
Format Journal Article
LanguageRussian
Published Russia (Federation) 2012
Subjects
Aged
Apoptosis - genetics
Case-Control Studies
DNA Mutational Analysis
fas Receptor - genetics
Female
Flow Cytometry
Humans
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
Lymphocytes - metabolism
Lymphocytes - pathology
Male
Middle Aged
Mutation
Parkinson Disease - genetics
Parkinson Disease - pathology
Protein-Serine-Threonine Kinases - genetics
Proto-Oncogene Proteins c-bcl-2 - genetics
Real-Time Polymerase Chain Reaction
Russia
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Summary:Mutations in the Leucine Reach Repeat Kinase 2 (LRRK2) gene are the most frequent cause of familial Parkinson's disease (PD). Although the precise physiological and pathological role of LRRK2 is unclear, a direct link between mutant LRRK2 and apoptosis has been suggested. Using flow cytometric analysis (PI+Annexin V(FITC)) we showed increased spontaneous apoptosis of peripheral blood lymphocytes in patients with LRRK.2-associated PD compared to controls after 24 (P < 0.016) and 48 (P < 0.031 ) h of incubation (5 % CO2, 37 degrees C). We found the increased FAS mRNA level in peripheral blood lymphocytes of patients with LRRK2-associated PD compared to controls (P < 0.05) and to sporadic PD (sPD) (P < 0.002). Significant difference in FAS expression between patients with LRRK2-associated PD and controls remained after three years and was detected after 1 and 24 h during lymphocyte incubation (P < 0.03 and 0.05, respectively). Increased spontaneous lymphocytes apoptosis along to increased FAS expression in patients with LRRK2-associated PD suggest that LRRK2 mutations may lead to the activation of extrinsic apoptotic way.
ISSN:0041-3771