A non-peptidyl neurotrophic small molecule for midbrain dopaminergic neurons.

Abstract

Abstract A small organic molecule (CUR-162590) that selectively enhances survival of midbrain dopaminergic neurons was identified by screening small molecule compound libraries. In embryonic midbrain cultures, CUR-162590 increased dopamine uptake and the number of dopaminergic neurons without altering the number of total neurons or astroglia or the uptake of GABA or serotonin. CUR-162590 reduced apoptosis of cultured dopaminergic neurons and protected against death induced by toxins such as MPP(+). Several synthetic analogs of CUR-162590 also had similar bioactivities. CUR-162590 thus represents a new class of neurotrophic small molecules that may have utility in the treatment of Parkinson's disease, which is marked by degeneration of midbrain dopaminergic neurons.

• Authors: Leu-Fen H Lin, Lee L Rubin, Mei Xu
• Journal: Journal of neurochemistry (J Neurochem) Vol. 89 Issue 6 Pg. 1387-95 (Jun 2004) ISSN: 0022-3042 [Print] England
• PMID: 15189341 (Publication Type: Comparative Study, Journal Article)

Chemical References

• CUR 162590
• Gdnf protein, rat
• Glial Cell Line-Derived Neurotrophic Factor
• Nerve Growth Factors
• Neuroprotective Agents
• Neurotoxins
• Sulfonamides
• Thiazoles
• Colforsin
• Serotonin
• Tyrosine 3-Monooxygenase
• 1-Methyl-4-phenylpyridinium
• Dopamine

Topics

• 1-Methyl-4-phenylpyridinium (toxicity)
• Animals
• Apoptosis (drug effects)
• Astrocytes (cytology, drug effects)
• Cell Count
• Cell Survival (drug effects)
• Cells, Cultured
• Colforsin (pharmacology)
• Dopamine (metabolism, pharmacokinetics)
• Dose-Response Relationship, Drug
• Drug Evaluation, Preclinical
• Glial Cell Line-Derived Neurotrophic Factor
• Mesencephalon (cytology, drug effects, embryology)
• Nerve Growth Factors (pharmacology)
• Neurons (drug effects, metabolism)
• Neuroprotective Agents (pharmacology)
• Neurotoxins (toxicity)
• Rats
• Sensitivity and Specificity
• Serotonin (metabolism, pharmacokinetics)
• Sulfonamides (pharmacology)
• Thiazoles (pharmacology)
• Tyrosine 3-Monooxygenase (metabolism)