[ My intention with my blog is to simply collect articles of
interest to me for purposes of future reference. I do my best to indicate who has actually composed the
articles. NONE of the articles have been written by me. – Louis Sheehan ]
Researchers at Tel Aviv
University believe they have tracked down one of the main reasons for
the seizures, memory loss and cognitive impairment that Alzheimer’s
patients suffer. Following up on the finding may show the way toward a
cure for the debilitating disease that hobbles millions of seniors.
The
research shows how a molecular mechanism involving proteins interferes
with brain neuron function and shifts them into dangerous overdrive. The
discovery gives researchers a clue towards solving the Alzheimer’s
puzzle, according to Dr. Inna Slutsky of TAU’s Sackler Faculty of
Medicine and Sagol School of Neuroscience.
“We have now identified the molecular players
in hyperactivity,” said Slutsky, adding that the discovery “may help to
restore memory and protect the brain.”
The effects of Alzheimer’s have been widely
observed — clumps of proteins build up in the brains of patients,
interfering with cognitive functions. The challenge has been to find the
mechanism behind the progression.
Slutsky published the results of a study on how brain hyperactivity affects Alzheimer’s patients in the latest edition of Cell Reports. The study was supported by European Research Council, Israel Science Foundation, and Alzheimer’s Association grants.
The culprit, according to research by
Slutsky’s team, appears to be enhanced neuronal activity in Alzheimer’s
patients, caused by a molecular mechanism involving amyloid precursor
protein (APP). APP is well-known by researchers for producing a
substance called amyloid-beta. APP also acts as a receptor for the
substance. According to the study, the binding of amyloid-beta to pairs
of APP molecules triggers a “signaling cascade,” in which messages
shared by brain cells are amplified, elevating neuronal activity and
essentially “short-circuiting” the brain’s communications network.
Doctors have observed this hyperactivity in
the hippocampus — the area of the brain that controls learning and
memory — among early stage Alzheimer’s patients, as well as in
individuals suffering from mild cognitive disorders, like poor memory.
Studies of mice have shown how the hyperactive hippocampal neurons
precede the formation of amyloid plaque — the protein clumps that may
block cell-to-cell signaling at synapses — leading to the eventual death
of brain cells and advanced Alzheimer’s.
In a five-year search for the underlying cause
of neuronal hyperactivity, TAU doctoral student Hilla Fogel and
postdoctoral fellow Samuel Frere found that amyloid-beta is essential
for the everyday transfer of information through the nerve cell
networks. However, if the level of amyloid-beta is even slightly
increased, it causes neuronal hyperactivity and greatly impairs the
effective transfer of information between neurons.
Using cutting-edge technology and in
collaboration with Prof. Joel Hirsch of TAU’s Faculty of Life Sciences,
Prof. Dominic Walsh of Harvard University, and Prof. Ehud Isacoff of
University of California Berkeley, the researchers found that the
binding of amyloid-beta triggers a change in the APP molecule
interactions, leading to an increase in calcium flux and higher
glutamate release — in other words, brain hyperactivity.
The problem emerges when too much of this
binding takes place — so the key, according to the research, is to
figure out a way to interfere with the binding of amyloid-beta to APP.
“TAU postdoctoral fellow Oshik Segev is now working to identify the
exact spot where the amyloid-beta binds to APP and how it modifies the
structure of the APP molecule,” said Slutsky. “If we can change the APP
structure and engineer molecules that interfere with the binding of
amyloid-beta to APP, then we can break up the process leading to
hippocampal hyperactivity. This may help to restore memory and protect
the brain.” Years of research are likely still needed before this
finding could be turned into practice.
Slutsky added, “One way of doing that may be a
reduction of an element called “tau” (microtubule-associated protein),
another key player in Alzheimer’s, which reverses synaptic deficits and
decreases abnormal brain activity in animal models. It will be crucial
to understand the missing link between APP and ‘tau’-mediated signaling
pathways leading to hyperactivity of hippocampal circuits. If we can
find a way to disrupt the positive signaling loop between amyloid-beta
and neuronal activity, it may rescue cognitive decline and the
conversion to Alzheimer’s disease.”
Posted but not written by: Lou Sheehan
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