Analysis of transcriptional profiles and functional clustering of global cerebellar gene expression in PCD3J

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• 作者：Gregory D. Ford ; Byron D. Ford ; Ernest C. Steele Jr. ; Alicia Gates ; Darryl Hood ; Mika A.B. Matthews ; Sophia Mirza ; Peter R. MacLeish
• 关键词：Apoptosis ; Kinase ; Microarray ; Neurodegeneration ; Purkinje cell
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2008
• 出版时间：12 December 2008
• 年：2008
• 卷：377
• 期：2
• 页码：556-561
• 全文大小：396 K

文摘

The Purkinje cell degeneration (PCD) mutant mouse is characterized by a degeneration of cerebellar Purkinje cells and progressive ataxia. To identify the molecular mechanisms that lead to the death of Purkinje neurons in PCD mice, we used Affymetrix microarray technology to compare cerebellar gene expression profiles in pcd3J mutant mice 14 days of age (prior to Purkinje cell loss) to unaffected littermates. Microarray analysis, Ingenuity Pathway Analysis (IPA) and expression analysis systematic explorer (EASE) software were used to identify biological and molecular pathways implicated in the progression of Purkinje cell degeneration. IPA analysis indicated that mutant pcd3J mice showed dysregulation of specific processes that may lead to Purkinje cell death, including several molecules known to control neuronal apoptosis such as Bad, CDK5 and PTEN. These findings demonstrate the usefulness of these powerful microarray analysis tools and have important implications for understanding the mechanisms of selective neuronal death and for developing therapeutic strategies to treat neurodegenerative disorders.