NWPF

News ArchivesRead News

New drug protects neurons in Parkinson's patients

Wednesday September 12, 2012

Scientists at Emory University School of Medicine have identified a compound that boosts levels of a survival factor in neurons threatened by Parkinson's disease.

Medical Press - The compound, bis-3-cognitin, could be a starting point for finding drugs that delay Parkinson's disease progression. Bis-3-cognitin appears to protect mitochondria, critical sites of vulnerability for neurons affected by Parkinson's.

In a widely used animal model of Parkinson's, bis-3-cognitin could protect neurons from damaging toxins and prevent mice from developing motor problems when it was given together with the toxin. The results were published online August 13 by the Journal of Biological Chemistry.

Zixu Mao, professor of pharmacology and neurology at Emory University School of Medicine, and his colleagues had been studying MEF2D, a protein that is vital for the survival of neurons. The first author of the paper, graduate student Lu Yao, is now at Xi'an Jiaotong University in China. Collaborators include Yifan Han and his colleagues at Hong Kong Polytechnic University.

Mao's previous research had shown that MEF2D is perturbed 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. You can search through a library of small molecules, or you can look through the literature and make a guess."

Bis-3-cognitin appears to have been a good guess, even though it was originally developed for a different purpose. The 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. The bis-cognitins have two tacrine molecules connected by a flexible chain.

Bis-3-cognitin could protect cells in culture against damage coming from the toxin MPTP, which mimics the effects of Parkinson's, by increasing MEF2D levels in the cells' nuclei and mitochondria. Tacrine and bis-7-cognitin, which has a longer connecting chain than bis-3-cognitin, did not have the same effects.

MPTP kills dopamine-responsive neurons, which are the same cells affected in Parkinson's. In mice, the scientists gauged the toxin's behavioral effects by measuring how long mice were able to hang on to a rotating rod, and studying their gait. Bis-3-cognitin, when given together with MPTP, could prevent motor impairment in the mice.

"We think MEF2D is not the only target of bis-3-cognitin," Mao says. "It is a potent antioxidant, for example. 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 appears to avoid the acute toxicity problems of tacrine, but more pharmacological studies of bis-3-cognitin's properties and mode of action are needed before human clinical trials.

More information: L. Yao et al. Activation of transcription factor MEF2 by bis(3)-cognitin protects dopaminergic neurons and ameliorates Parkinsonian motor defects. J. Biol Chem. (2012). www.jbc.org/cgi/do… .M112.367540 Journal reference: Journal of Biological Chemistry Provided by Emory University

Recent News

Sep 19 - PD protein plays vital 'marshalling' role in healthy brains
Sep 14 - Is it Alzheimer's or another type of dementia?
Sep 13 - Stem cells injected into brain of patient
Sep 11 - Can yoga help Parkinson's patients?
Sep 8 - Can some types of fat protect us from brain disease?
Sep 8 - Common molecular mechanism of Parkinson's pathology discovered
Sep 6 - Virtual Reality Test Could Make It Easier To Diagnose MS And Parkinson’s
Sep 5 - Seattle hospital offers new treatment to stop shaking
Aug 29 - The Decline of Tube Feeding for Dementia Patients
Aug 28 - New test may help detect Parkinson's disease in early stages of illness
Aug 25 - Stealthy Biotech Revives Stalled Parkinson's Drug, Reveals Plans In Alzheimer's and ALS
Aug 22 - Parkinson's Disease Could Be Diagnosed Through Eye Check, Mice Help Researchers In Further Study
Aug 22 - Machine learning to unlock Parkinson's disease mystery
Aug 22 - Manufacturing Dopamine in the Brain with Gene Therapy
Aug 21 - Cognitive control plays major role in Parkinson’s Gait
Aug 15 - 'I've Never Felt Constrained': After Parkinson's Diagnosis, Chestnut Hill Man Turns To Drumming
Aug 11 - Virtual reality and treadmill training could help prevent falls in older adults
Aug 9 - New laboratory model replicates early phase of Parkinson's before onset of motor symptoms
Aug 8 - Marshall University Scientists Develop A New Approach For Parkinson’s Disease Therapy
Aug 5 - Cambuslang woman diagnosed with Parkinson's at 42 is set to trek through Alps