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Genomic and proteomic study to survey the mechanism of action of the anti-Parkinson's disease drug, rasagiline compared with selegiline, in the rat midbrain.

Abstract
The novel anti-Parkinson's disease (PD) drug, rasagiline (N-propargyl-1-(R)-aminoindan), is a second generation of irreversible selective inhibitor of monoamine oxidase-B follows selegiline. In light of the recent large clinical study (phase III ADAGIO) reporting benefits in PD patients, it has been suggested that rasagiline could be the first PD treatment to receive the label neuroprotective "disease-modifying" drug. Indeed, rasagiline has been shown to have a broad neuroprotective activity against a variety of neurotoxins in preclinical models of neurodegenerative diseases and in cultured neuronal cells. In the present study, we have investigated the status of various molecular and biochemical markers in the rat midbrain following chronic treatments with rasagiline and selegiline, using proteomic and genomic analyses. Our findings demonstrated significant molecular changes induced by both drugs, at the protein and transcriptional levels, associated with neuronal differentiation, cell survival and death pathways, metabolism/oxidation stress, signaling system, and biomarkers of neurodegenerative disorders, which may be reflected in the clinical studies.
AuthorsOrly Weinreb, Tamar Amit, Yotam Sagi, Noam Drigues, Moussa B H Youdim
JournalJournal of neural transmission (Vienna, Austria : 1996) (J Neural Transm (Vienna)) Vol. 116 Issue 11 Pg. 1457-72 (Nov 2009) ISSN: 1435-1463 [Electronic] Austria
PMID19396396 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antiparkinson Agents
  • Biomarkers
  • Indans
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • rasagiline
  • Selegiline
Topics
  • Animals
  • Antiparkinson Agents (pharmacology)
  • Biomarkers (analysis, metabolism)
  • Cell Survival (drug effects, physiology)
  • Female
  • Genomics (methods)
  • Indans (pharmacology)
  • Nerve Growth Factors (genetics, metabolism)
  • Nerve Tissue Proteins (drug effects, genetics, metabolism)
  • Neurogenesis (drug effects, physiology)
  • Neuroprotective Agents (pharmacology)
  • Parkinson Disease (drug therapy, genetics, metabolism)
  • Proteomics (methods)
  • Rats
  • Rats, Wistar
  • Selegiline (pharmacology)
  • Signal Transduction (drug effects, physiology)
  • Substantia Nigra (drug effects, metabolism, physiopathology)

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