Novel Therapeutics for Parkinson's Disease
- 技术优势
- Only selective antagonists of the Cav 1.3 pore in calcium channels Orally bioavailable Blood-brain barrier penetration
- 详细技术说明
- Potent and selective antagonists of the Cav 1.3 calcium channel with neuroprotective potential.#therapeutics #cns #parkinsonsdisease
- *Abstract
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Northwestern researchers have identified the L-type calcium channel, Cav 1.3, as a target for potential treatment of Parkinson's disease (PD). In addition, they have developed pyrimidine 2,4,6 triones that are novel and selective antagonists of Cav 1.3 channels. The most vulnerable population of neurons in PD, the substantia nigra pars compacta (SNc) dopamine neurons, have a distinctive phenotype that leads to sustained mitochondrial oxidant stress. This stress originates from a sustained calcium influx through a distinctive channel in the membrane of the SNc dopamine neurons. Use of dihydropyridine, a targeted antagonist of these channels, diminishes the risk of PD in humans, however, these antagonists exhibit some non-selective effects. In particular, this older group of compounds binds to calcium channels in the cardiovascular system resulting in potentially life-threatening adverse events and limiting their utility as a neuroprotective agent.The novel pyrimidine antagonists developed at Northwestern could serve as potent neuroprotective agents for Parkinson's disease and other aging-related neurodegenerative diseases, such as Alzheimer's disease.
- *Inventors
- Dalton J. Surmeier, Jr.* Richard B. Silverman* Soosung Kang Garry Cooper
- 国家/地区
- 美国
