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

Yalcinkaya N., Haytural H., BİLGİÇ B., Ozdemir Ö. , Hanagasi H., KÜÇÜKALİ C. İ. , ...More

NEUROSCIENCE LETTERS, vol.615, pp.72-77, 2016 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 615
  • Publication Date: 2016
  • Doi Number: 10.1016/j.neulet.2016.01.029
  • Title of Journal : NEUROSCIENCE LETTERS
  • Page Numbers: pp.72-77


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.