Scientists from Karolinska Institutet and Seville University, working with colleagues at Lund University, found they could prevent inflammation linked to neurodegenerative diseases by blocking enzymes called caspases. They found that these enzymes control the activation of microglial cells.
Details of the study are reported in “Caspase signaling controls microglia activation and neurotoxicity,” published in Nature on March 9.
Past studies have suggested that microglial cells play a critical part in neurodegenerative diseases. The over-activation of these cells in the brain can cause inflammation, resulting in neuronal death.
Studying cell cultures and mice, the researchers showed that certain caspases (3, 7, and 8) activate rather than kill microglial cells, triggering an inflammatory reaction resulting in neuronal death. Mice given caspase inhibitors displayed fewer activated microglia as well as less inflammation and cell death in the surrounding neurons.
The researchers also examined samples from deceased Alzheimer disease and Parkinson disease patients. They discovered a higher incidence of activated caspases in their microglial cells.
"We'll now be examining whether the substances that inhibit the caspases can be candidates for useful drugs in the treatment of certain neurological diseases," says Bertrand Joseph, Ph.D., a Karolinska associate professor who headed the study.