Neuroscientist from the University of California, Santa Barbara synthesized a drug which cures the pathological characteristics of brains from mice with neurodegenerative diseases. The study, published in The Journal of Biological Chemistry, adds a new tool in the arsenal of therapies of tauopathies, i.e. diseases such as Alzheimer’s.
Our cells require enzymes to make chemical reactions constantly. Kinases is a class of these enzymes and the result of such chemical reactions is the modification of certain proteins. In the brains of patients with neurodegenerative diseases, the kinase cdk5 is hyper active and modifies a protein called tau, a protein with numerous important functions in brain neurons. But when modified by cdk5, tau forms tangles and cannot function. The most common characteristic of patients with Alzheimer’s disease, for example, is the formation of neurofibrillary tangles (NFTs) made of aggregates of modified tau.
Obviously, one of the most promising strategy for treatment is to find a way to stop cdk5 from modifying tau. Therefore, scientists are trying to develop drugs to block this enzyme. In 2005, neuroscientists in the laboratory of Kenneth Kosik have developed a drug which inhibits cdk5, but now they have synthesized a better version. In the new study, Xuemei Zhang and Israel Hernandez with their colleagues have used this improved compound, termed diaminothiazole, and found that only small concentrations can block cdk5. This allowed them to use small amounts so that it would not be toxic in vivo. Indeed, when they injected mouse models of neurodegenerative diseases, they saw that the NFTs disappeared and the brain neurons looked healthy again. This was mainly the result of tau not being modified, suggesting that diaminothiazoles work as planned, to block tau from forming tangles and offer neuroprotection. The treated mice also showed improvement in memory and behaviour tests in the lab.
However, cdk5 is not the only enzyme that modifies tau. GSK-3 for example is another one, even though it requires cdk5 to act first and then GSK-3 follows Maybe the success of diaminothiazoles is behind the fact that cdk5 is the master enzyme for tau modification and NFT formation. “Effective treatment of tauopathies may require dual kinase targeting.” Kosik acknowledges and follow-up clinical studies would show whether diaminothiazole alone or in combination with other drugs could be a possible therapeutic strategy for neurodegenerative diseases.