Gene and Protein Expression Profiling in Parkinson's Disease: Quest for Neuroprotective Drugs
In spite of the extensive studies performed on postmortem substantia nigra (SN) of Parkinson's disease (PD) brains, the etiology of the disease has not yet been established. The identification of single mutated genes linked to heritable forms of PD has fu
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Gene and Protein Expression Profiling in Parkinson’s Disease: Quest for Neuroprotective Drugs
O. Weinreb . T. Amit . E. Gru¨nblatt . P. Riederer . M. Youdim . S. Mandel
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 2 Gene Expression Profiling in PD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 3 Interpretation of Microarray Gene Profiling Results from Human PD Brains . . . . . . . . . . . . . . . . . . . . 68 4 Gene and Protein Expression Profiling of the Neuroprotective, Anti‐PD Drug, Rasagiline . . . . . . 69 5 Transcriptomics and Proteomics in the Aging Brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 6 ‘‘All Roads Lead to Rome’’ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 7 Conclusions and Future Directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
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Springer-Verlag Berlin Heidelberg 2007
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Gene and protein expression profiling in Parkinson’s disease: Quest for neuroprotective drugs
Abstract: In spite of the extensive studies performed on postmortem substantia nigra (SN) of Parkinson’s disease (PD) brains, the etiology of the disease has not yet been established. The identification of single mutated genes linked to heritable forms of PD has further enlightened our understanding of its etio‐ pathophysiology in the nongenetic cases providing potential molecular pathways associated with those genes. There is a recognized consensus that in both the genetic and sporadic cases of PD there is a crucial implication of mitochondria and ubiquitin‐proteasome system dysfunction that expresses itself with excess production of reactive oxygen species, protein misfolding, and aggregation into inclusion bodies. However, the precise identity of the pivotal genes involved in the neurotoxic cascade pathways leading to the death of the dopaminergic neurons in sporadic PD, which constitutes around 90% of the total cases of the disease, is still unknown. This chapter will review recent large‐scale microarray gene expression profiling studies in human postmortem SN from sporadic PD brains and highlight gene candidates as putative molecular signatures for early diagnosis and future development of CNS ‘‘magic bullets’’ personalized drugs. We will discuss the application of transcriptomics and proteomics in the quest for neuroprotective drugs that might possess disease‐modifying action. List of Abbreviations: ADH5, alcohol dehydrogenase 5; BDNF, brain‐derived neurotrophic factor; CDC42, cell division cycle 42; COX, cytochrome c oxidase; CSK, c‐src tyrosine kinase; DAT, dopamine transporter; EGLN1, egl nine homolog 1; GADPH, glyceraldehyde 3‐
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