Researchers at the University of Toronto believe they're one step closer to unravelling the mystery of Alzheimer's disease, opening new avenues in the quest for a cure.
Investigating the role calcium plays in the degenerative brain disease, two biologists have found a theoretical link between the protein calmodulin — which can be inhibited using existing drugs — and Alzheimer's.
“Calmodulin acts like a switch, it turns other proteins on or off,” said professor Danton O'Day. “When it detects too much calcium, it activates and deactivates things it shouldn't.”
Some 364,000 Canadians over 65 suffer from Alzheimer's disease and related dementia, according to the Alzheimer Society of Canada. Although the exact cause is unknown, one of the primary theories is that unregulated calcium levels in the brain lead to nerve cell dysfunction and death.
Prof. O'Day and colleague Michael Myre wanted to see if calmodulin, given its relationship with calcium, played a role. They discovered that 60 to 80 per cent of the primary proteins connected to Alzheimer's disease were — theoretically — regulated by calmodulin.
“The next step is to verify the (role of) calmodulin . . . by doing some experimentation,” said Prof. O'Day. “We're talking with people about doing that now.”
If the theory holds, existing calmodulin-inhibiting drugs could be used to delay the onset of — and perhaps eventually prevent — Alzheimer's, said Prof. O'Day.
“The inhibitors would be stopping one of the pathways that calcium is activating,” he said. “You would be, in a sense, stopping the downstream effects of the misfiring of neurons and also cell death.”
In the meantime, there's no need for people to worry about how much calcium they're consuming. In fact, calcium is essential for brain function, among other things. It's only when the brain cells become “leaky” and thus permeable to calcium — as in the case of Alzheimer's — that it becomes an issue, said Prof. O'Day.
The researchers hope the findings — to be published in the Aug. 6 issue of Biochemical and Biophysical Research Communications — will provide a new avenue for Alzheimer's research. At the same time, Prof. O'Day cautions that it's only one step toward a possible cure.
“Anything that moves you one step forward is always important,” he said. “But we never know how many steps there are until it's done.”
