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New Drugs Against Alzheimer's Disease

  April, 28 2001 3:35
your information resource in human molecular genetics
Fréderic Checler from the Institut de Pharmacologie Moleculaire et Cellulaire in Nice, France and Jean-Louis Kraus from Trophos, Inc., Marseille, France now describe in the May issue of Nature Cell Biology (Vol. 3, No. 5), new synthetic drugs that specifically target what may be the causal event of Alzheimer’s disease (AD), without any obvious side effects.

Patients with Alzheimer’s disease (AD) accumulate aggregates of the Amyloid-Beta protein (A-Beta) in their brain. Whether this is a cause or a consequence of the disease is still a matter of debate, but there is some evidence supporting the former hypothesis: when incubated with A-Beta in vitro, neurons die and immunization with A-Beta seems to vaccinate mice from AD.

A-Beta is the product of cleavage of its precursor, amyloid precursor protein, by an enzyme called Gamma-secretase. Blocking this enzyme might, therefore, prevent the accumulation of A-Beta and hence the progression of AD.

But, as Gamma-secretase has other substrates (such as the Notch protein and possibly the Ire1 protein) which are involved in essential processes such as defence, cell differentiation and response to stress, drugs developed to block it might have undesirable secondary effects.

Checler and Kraus have now synthesized new drugs that specifically affect A-Beta generation by Gamma-secretase, without affecting Gamma-secretase cleavage of other substrates.


Frederic Checler
tel + 33 4 93 95 7760
e-mail checler@ipmc.cnrs.fr

Jean-Louis Kraus
tel + 33 4 91 82 91 41
e-mail kraus@luminy.univ-mrs.fr

(C) Nature Cell Biology press release.

Message posted by: Trevor M. D'Souza

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