RyR2 as a Target to Prevent Alzheimer's Symptoms in a Mouse Model of the Condition
Mouse models of Alzheimer's disease are quite artificial: mice, and indeed most mammals, do not naturally exhibit the relevant mechanisms underlying Alzheimer's disease, such as aggregation of amyloid-β. The details of the model become important in determining whether or not discoveries and interventions are relevant in anything other than the model. Thus one shouldn't become too excited by any small adjustment to cellular metabolism that appears to have profound effects on the progression of the condition in these models. Maybe it will be relevant to the human condition, but the odds are not good, looking at the history of this sort of thing. Still, the size of the effect in this case is quite interesting.
Researchers discovered that limiting the open time of a channel called the ryanodine receptor, which acts like a gateway to cells located in the heart and brain, reverses and prevents progression of Alzheimer's disease in animal models. A single RyR2 point mutation, which reduces RyR2 open time, prevents hyperexcitability, hyperactivity, memory impairment, neuronal cell death, and dendritic spine loss in an Alzheimer's disease mouse model.
Researchers also identified a drug, derived from the heart medication carvedilol, that interrupts the disease process by reducing the open type of the ryanodine receptor. The effect of giving the drug to animal models was remarkable: After one month of treatment, the memory loss and cognitive impairments in these models disappeared.
Previous research has shown that the progression of Alzheimer's disease is driven by a vicious cycle of the protein amyloid β (Aβ) inducing hyperactivity at the neuron level. However, the mechanism behind this wasn't fully understood nor were there effective treatments to stop the cycle. Here, the team used a portion of an existing drug used for heart patients, carvedilol, to treat mice models with Alzheimer's symptoms. "We treated them for a month and the effect was quite amazing. We couldn't tell the drug-treated disease models and the healthy models apart."