Peripheral expression of key regulatory kinases in Alzheimer's disease and Parkinson's disease

被引:42
作者
Armentero, M. T. [1 ]
Sinforiani, E. [2 ]
Ghezzi, C. [1 ]
Bazzini, E. [1 ]
Levandis, G. [1 ]
Ambrosi, G. [1 ]
Zangaglia, R. [3 ]
Pacchetti, C. [3 ]
Cereda, C. [4 ]
Cova, E. [4 ]
Basso, E. [4 ]
Celi, D. [5 ]
Martignoni, E. [6 ]
Nappi, G. [7 ]
Blandini, F. [1 ]
机构
[1] IRCCS Neurol Inst C Mondino, Interdept Res Ctr Parkinsons Dis, Lab Funct Neurochem, I-27100 Pavia, PV, Italy
[2] IRCCS Neurol Inst C Mondino, Interdept Res Ctr Parkinsons Dis, Alzheimers Dis Assessment Unit, I-27100 Pavia, PV, Italy
[3] IRCCS Neurol Inst C Mondino, Interdept Res Ctr Parkinsons Dis, Ctr Parkinsons Dis & Movement Disorders, I-27100 Pavia, PV, Italy
[4] IRCCS Neurol Inst C Mondino, Lab Expt Neurobiol, I-27100 Pavia, PV, Italy
[5] IRCCS Ctr Neurolesi Bonino Pulejo, Messina, Italy
[6] Univ Insubria, Dept Clin Med, Varese Neurorehabil & Movement Disorders Unit, IRCCS Fdn S Maugeri, Tradate, Italy
[7] Univ Roma La Sapienza, Chair Neurol, Rome, Italy
关键词
Glycogen kinase 3; Protein kinase B; Tau; Neurodegenerative disease; Peripheral blood lymphocytes; GLYCOGEN-SYNTHASE KINASE-3; TAU-PROTEIN; CEREBROSPINAL-FLUID; BLOOD-LYMPHOCYTES; OXIDATIVE STRESS; BETA-CATENIN; L-DOPA; AKT; GLYCOGEN-SYNTHASE-KINASE-3; PHOSPHORYLATION;
D O I
10.1016/j.neurobiolaging.2010.01.004
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Alteration of key regulatory kinases may cause aberrant protein phosphorylation and aggregation in Alzheimer's disease (AD) and Parkinson's disease (PD). In this study, we investigated expression and phosphorylation status of glycogen synthase kinase 3 (GSK-3), protein kinase B (Akt) and tau protein in peripheral blood lymphocytes of 20 AD, 25 PD patients and 20 healthy controls. GSK-3 was increased in AD and PD patients. In these latter, GSK-3 levels were positively correlated with daily L-Dopa intake. Phosphorylated Akt expression was augmented in both groups; total Akt levels were increased only in AD patients and were positively correlated with disease duration and severity. Total and phosphorylated tau were increased only in AD, with phospho-tau levels being positively correlated with levels of total tau, Akt, and disease duration. No correlations between protein levels and clinical variables were found in PD patients. Investigation of peripheral changes in the expression of specific kinases may, therefore, lead to the development of innovative biomarkers of neurodegeneration, particularly for AD. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:2142 / 2151
页数:10
相关论文
共 46 条
  • [1] GSK3α exhibits β-catenin and tau directed kinase activities that are modulated by Wnt
    Asuni, Ayodeji A.
    Hooper, Claudie
    Reynolds, C. Hugh
    Lovestone, Simon
    Anderton, Brian H.
    Killick, Richard
    [J]. EUROPEAN JOURNAL OF NEUROSCIENCE, 2006, 24 (12) : 3387 - 3392
  • [2] Specific tau phosphorylation sites correlate with severity of neuronal cytopathology in Alzheimer's disease
    Augustinack, JC
    Schneider, A
    Mandelkow, EM
    Hyman, BT
    [J]. ACTA NEUROPATHOLOGICA, 2002, 103 (01) : 26 - 35
  • [3] The Akt-GSK-3 signaling cascade in the actions of doparnine
    Beaulieu, Jean-Martin
    Gainetdinov, Raul R.
    Caron, Marc G.
    [J]. TRENDS IN PHARMACOLOGICAL SCIENCES, 2007, 28 (04) : 166 - 172
  • [4] Incipient Alzheimer's disease: Microarray correlation analyses reveal major transcriptional and tumor suppressor responses
    Blalock, EM
    Geddes, JW
    Chen, KC
    Porter, NM
    Markesbery, WR
    Landfield, PW
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (07) : 2173 - 2178
  • [5] Peripheral proteasome and caspase activity in Parkinson disease and Alzheimer disease
    Blandini, F
    Sinforiani, E
    Pacchetti, C
    Samuele, A
    Bazzini, E
    Zangaglia, R
    Nappi, G
    Martignoni, E
    [J]. NEUROLOGY, 2006, 66 (04) : 529 - 534
  • [6] Modifications of apoptosis-related protein levels in lymphocytes of patients with Parkinson's disease. The effect of dopaminergic treatment
    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
    [J]. JOURNAL OF NEURAL TRANSMISSION, 2004, 111 (08) : 1017 - 1030
  • [7] Toxin-induced models of Parkinson's disease
    Bové J.
    Prou D.
    Perier C.
    Przedborski S.
    [J]. NeuroRX, 2005, 2 (3): : 484 - 494
  • [8] PI3-K and GSK-3: Akt-ing together with microtubules
    Buttrick, Graham J.
    Wakefield, James G.
    [J]. CELL CYCLE, 2008, 7 (17) : 2621 - 2625
  • [9] Dopamine depletion and subsequent treatment with L-DOPA, but not the long-lived dopamine agonist pergolide, enhances activity of the Akt pathway in the rat striatum
    Bychkov, Evgeny
    Ahmed, M. Rafiuddin
    Dalby, Kevin N.
    Gurevich, Eugenia V.
    [J]. JOURNAL OF NEUROCHEMISTRY, 2007, 102 (03) : 699 - 711
  • [10] Glycogen synthase kinase 3β phosphorylates tau at both primed and unprimed sites -: Differential impact on microtubule binding
    Cho, JH
    Johnson, GVW
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (01) : 187 - 193