2024-03-29T10:46:02Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1087912020-11-13T13:13:35Zcom_10261_86com_10261_1col_10261_339
Esteras, Noemí
Alquézar, Carolina
Bartolomé Robledo, Fernando
De la Encarnación, Ana
Bermejo-Pareja, Félix
Molina, J.A.
Martín-Requero, Ángeles
2014-09-03
Molecular Neurobiology, 2014
0893-7648
http://hdl.handle.net/10261/108791
10.1007/s12035-014-8870-y
1559-1182
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease among aging individuals, affecting greatly the quality of their life. However, the
pathogenesis of Parkinson's disease is still incompletely understood to date. Increasing experimental evidence suggests that cell cycle reentry of postmitotic neurons precedes many instances of neuronal death. Since cell cycle dysfunction is
not restricted to neurons, we investigated this issue in peripheral cells from patients
suffering from sporadic PD and age-matched control individuals. Here, we describe
increased cell cycle activity in immortalized lymphocytes from PD patients, that is
associated to enhanced activity of the cyclin D3/CDK6 complex, resulting in higher
phosphorylation of the pRb family protein and thus, in a G1/S regulatory failure. Decreased degradation of cyclin D3, together with increased p21 degradation, as well as elevated levels of CDK6 mRNA and protein were found in PD lymphoblasts. Inhibitors of cyclin D3/CDK6 activity like sodium butyrate, PD-332991, and rapamycin were able to restore the response of PD cells to serum stimulation. We conclude that lymphoblasts from PD patients are a suitable model to investigate cell biochemical aspects of this disease. It is suggested that cyclin D3/CDK6-associated kinase activity could be potentially a novel therapeutic target for the treatment of PD.
eng
openAccess
Parkinson disease
Lymphocytes
Cell cycle
pRb
CDK6
TDP-43
Cyclin D3
Rapamycin
Sodium butyrate
PD-332991
G1/S cell cycle checkpoint dysfunction in lymphoblasts from sporadic Parkinson’s disease patients.
artículo