Alterations in cyclin-dependent protein kinase 5 (CDK5) protein levels, activity and immunocytochemistry in canine motor neuron disease.
Alterations in cyclin-dependent protein kinase 5 (CDK5) protein levels, activity and immunocytochemistry in canine motor neuron disease.
复制标题
犬运动神经元疾病中细胞周期蛋白依赖性蛋白激酶 5 (CDK5) 蛋白水平、活性和免疫细胞化学的变化。
DOI：
10.1097/00005072-199811000-00010
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发表时间：
1998
影响因子：
3.2
通讯作者：
Cork,LC
中科院分区：
文献类型：
--
作者：
Green,SL;Vulliet,PR;Pinter,MJ;Cork,LC
Hereditary canine spinal muscular atrophy (HCSMA) is a dominantly inherited motor neuron disease in Brittany spaniels that is clinically characterized by progressive muscle weakness leading to paralysis. Histopathologically, degeneration is confined to motor neurons with accumulation of phosphorylated neurofilaments in axonal internodes. Cyclin-dependent kinase 5 (CDK5), a kinase related to the cell cycle kinase cdc2, phosphorylates neurofilaments and regulates neurofilament dynamics. We examined CDK5 activity, protein levels, and cellular immunoreactivity in nervous tissue from dogs with HCSMA, from closely age-matched controls and from dogs with other neurological diseases. On immunoblot analysis, CDK5 protein levels were increased in the HCSMA dogs (by ∼ 1.5-fold in both the cytosolic and the particulate fractions). CDK5 activity was significantly increased (by ∼3-fold) in the particulate fractions in the HCSMA dogs compared to all controls. The finding that CDK5 activity was increased in the young HCSMA homozygotes with the accelerated form of the disease, who do not show axonal swellings histologically, suggests that alterations in CDK5 occurs early in the pathogenesis, prior to the development of significant neurofilament pathology. Immunocytochemically, there was strong CDK5 staining of the nuclei, cytoplasm and axonal processes of the motor neurons in both control dogs and dogs with HCSMA. Further immunocyto-chemical studies demonstrated CDK5 staining where neurofilaments accumulated, in axonal swellings in the dogs with HCSMA. Our observations suggest phosphorylation-dependent events mediated by CDK5 occur in canine motor neuron disease.
