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Neurological conditions / acetylcholine
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PostPosted: Sat Jul 30, 2005 4:50 pm    Post subject: Neurological conditions / acetylcholine Reply with quote

Anti-inflammatory function of Alzheimer's disease drugs revealed
29 Jul 2005

The mechanism in anti-Alzheimer's disease drugs that inhibits the
production of a destructive, inflammation-causing protein in the brain
has been revealed by researchers at the Hebrew university of Jerusalem.

Their work, described in a recent issue of the American journal, Annals
of Neurology, is likely to lead to the development of more efficient
drugs than are currently in use for treating Alzheimer's Disease as
well as other neurological conditions resulting from infections,
autoimmune diseases such as multiple sclerosis, or brain inflammation
resulting from trauma or stroke.

The research team working on this project was headed by Prof. Raz
Yirmiya of the Psychology Department at the Hebrew University, Dr.
Yehuda Pollak, a post-doctoral fellow in Prof. Yirmiya's laboratory;
and in cooperation with Hermona Soreq, the Charlotte Slesinger
Professor of Cancer Studies at the Silberman Institute of Life Sciences
at the Hebrew University, and Prof. Tamir Ben-Hur of the Hebrew
University Faculty of Medicine.

Alzheimer's Disease is a degenerative disease of the brain,
characterized by a deterioration of both cognitive and physical
abilities. It first affects memory and the ability to carry out
complex, coordinated tasks. It also can bring on depression,
inattention and outbursts of anger. In a more progressive stage, the
disease can cause difficulties in the ability to perform even simple
tasks such as speaking and comprehending, eating and sleeping. The
affected person can even forget his name and identity.

The medicines administered today to Alzheimer's Disease patients focus
on preventing the breakdown of acetylcholine, a chemical produced by
brain cells which transmits information within the brain and is vitally
involved in cognitive processes that include memory, attention and
thought. Because acetylcholine-producing cells are among the first to
die in Alzheimer's Disease patients, drug-induced elevation of
acetylcholine levels partially attenuates the cognitive deterioration.

In recent years it has been shown that another pathological process
that occurs in the brain of Alzheimer's Disease patients is excessive
immune activation and inflammation, which are induced by overproduction
of an inflammation-producing protein called interleukin-1, as well as a
few other related compounds. This process can impair the functioning of
nerve cells and can even lead to their death. Furthermore, genetic
alterations in the interleukin-1 gene have been associated with
increased risk for the appearance and severity of Alzheimer's Disease

The Hebrew University researchers found that anti-Alzheimer's Disease
drugs currently in use not only block the activity of the enzyme
responsible for breaking down acetylcholine but also cause a marked
reduction in the production of interleukin-1. Furthermore, they
describe the use of a novel drug (EN101), developed by Prof. Soreq's
team, which produces these effects in a more efficient way than known
heretofore by destroying the molecular antecedent (messenger RNA) of
the enzyme, rather than simply blocking the enzyme's activity.

In a series of experiments, conventional anti-Alzheimer's Disease
drugs, as well as the novel drug EN101, were injected into mice with
brain inflammation. It was found that these injections reduced
significantly the activity of the enzyme that breaks down acetylcholine
and blocked almost entirely the production of interleukin-1.

"These findings suggest a new role for acetylcholine in the brain,"
said Prof. Yirmiya. "When the anti-Alzheimer's Disease drugs block the
enzyme which breaks down acetylcholine, the level of this chemical in
the brain goes up, and there is a reduction of the production of the
inflammatory material, interleukin-1, and its destructive influence in
the brain."

"The discovery of this mechanism in the anti-Alzheimer's Disease
medicines points the way towards development of new forms of these
medicines which will block even more efficiently and specifically the
inflammatory and destructive activity of inteleukin-1," Prof. Yirmiya
stressed. "Beyond that, it is likely that the drugs that are currently
used for treatment of Alzheimer's Disease, and particularly the new
drug EN101, will also be effective in dealing with other inflammatory

Jerry Barach
The Hebrew University of Jerusalem


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