New lead on drugs against Parkinson's disease
Emory scientists have identified a compound that boosts the survival of neurons threatened by Parkinson’s disease.
The compound, bis-3-cognitin, could be a starting point for finding drugs that delay Parkinson’s disease progression.
In mice, bis-3-cognitin could protect neurons from damaging toxins and from developing motor problems when it was given together with the toxin.
Zixu Mao, an Emory pharmacology researcher, and his colleagues had been studying MEF2D, a protein vital for the survival of neurons. Mao’s previous research had shown that MEF2D is altered in the neurons of people with Parkinson’s disease. The MEF2D protein is sensitive to cellular changes, such as oxidative stress, which can lead to neuron damage in Parkinson’s.
"For years, we had been talking about looking for drugs that enhance MEF2D," Mao says. "The challenge was how to set up a screening system."
Bis-3-cognitin appears to have been a good catch. Cognitins are a family of compounds derived from tacrine, the first drug approved by the FDA to treat the symptoms of Alzheimer’s disease. Tacrine was eventually discontinued because of liver toxicity and other side effects.
Bis-3-cognitin could protect cells in culture by increasing MEF2D levels. It also protected against the toxin MPTP, which kills neurons.
"We think MEF2D is not the only target of bis-3-cognitin," Mao says. "It is a potent antioxidant, but MEF2D is required for the neuroprotective activity—we found that if you knock down MEF2D in cell lines, the protective effects are much weaker."
He adds that bis-3-cognitin also appears to avoid the acute toxicity problems of tacrine.
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