Agents that inhibit the activity of gamma secretase
are now being studied as treatment for Alzheimer's disease.
APP is a large protein expressed in neurons that is cleaved into smaller proteins and peptides by several processing enzymes called secretases
With regard to APP intracellular processing, both secretases
([alpha]- and [beta]-) have been identified in the ER together with [gamma]-secretase which is present in mitochondria-associated membrane (MAM) subcompartment [48, 68].
(117) have shown that a cocktail of secretase
inhibitors affects A[beta] levels in an additive manner.
The company intends to file an IND on the lead modulator of gamma- secretase
The article on gamma secretase
and Notch highlights two molecules that are close to being detailed as targets but cannot be currently labelled as such.
The company announced semagacestat, a gamma secretase
inhibitor, endured two on-going long-term studies, during which the drug not only failed at slowing Alzheimer's progression, but also affected the ability to perform activities of daily living.
The pill semagacestat inhibits an enzyme called gamma secretase
thatAAEs tied to amyloid production.
"There is compelling evidence that sAPPbeta, the ectodomain of amyloid precursor protein (APP) shed through beta secretase
cleavage, is an important component in the pathogenesis of AD," said Joe Bertelsen, neuroscience product manager, Covance.
The findings, published in the journal Nature, show drugs called gamma secretase
modulators work to stop the build-up of a protein thought to trigger Alzheimer's.
The problem with most proposed methods of blocking beta secretase
, the study found, is that they are designed to work outside of the affected brain cells.
Recent ADDL discoveries could also contribute to research into potential antiamyloid therapies, which currently fall into three groups: immunotherapies that prompt the body's immune system to destroy A[beta], antiaggregants that keep the molecules from clumping, and enzyme (secretase
) modulators that prevent the creation of A[beta] or hasten its destruction.