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Expression changes of genes associated with apoptosis and survival processes in Parkinson's disease

Yazar
Gurvit, Hakan
Bilgic, Başar
Tuzun, Erdem
Kucukali, Cem Ismail
Hanagasi, Haşmet Ayhan
Haytural, Hazal
Ozdemir, Ozkan
OZBEK, Zeynep
Akcan, Ugur
Yalcinkaya, Nazli
Idrisoglu, Halil Atilla
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Özet
Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of the dopaminergic neurons in substantia nigra, presumably due to increased apoptosis and oxidative stress. To investigate whether PD-induced survival/apoptosis gene expression changes can serve as prognostic biomarkers of PD, we measured expression levels of phosphatidylinosito1-4,5-bisphosphate 3-kinase (PI3K)/Akt pathway factors and additional apoptotic and anti-apoptotic factors in peripheral blood mononuclear cells (PBMC) of PD patients (n = 50) and healthy controls (n = 50) by real time PCR. Expression levels of apoptotic factors phosphatase and tensin homolog (PTEN) and mitochondrial apoptosis-inducing factor 1 (AIFM1) were significantly decreased, anti-apoptotic factors DJ-1 and Akt-1 were significantly increased and anti-apoptotic Bcl-2 was significantly decreased in PD patients. Expression levels of AIFM1 were significantly correlated with Hoehn Yahr scores. Moreover, PD patients with postural instability showed significantly reduced expression levels of anti-apoptotic DJ-1, Akt-1 and mTOR than PD patients without postural instability. Expression profiles of brain samples of mice with rotenone-induced PD model and PBMC samples of PD patients showed remarkable resemblance. Our results indicate that the anti-apoptotic PI3K/Akt pathway is over activated in PD, presumably as an effort to compensate for increased neuronal apoptosis and oxidative stress. By contrast, patients with postural instability show reduced anti-apoptotic factor expression suggesting that this compensating mechanism fails in patients with this particular motor symptom. PBMC expression levels of AIFM1 might serve as a biomarker of disability and disease progression in PD. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
Bağlantı
http://hdl.handle.net/20.500.12627/87801
https://doi.org/10.1016/j.neulet.2016.01.029
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