Enzyme may be linked to Alzheimer’s
An enzyme found naturally in the brain snips apart the protein thatforms the sludge
called amyloid plaque that is one of the hallmarks ofAlzheimer’s disease (AD), researchers have found. They said theirfindings in mice suggest that the protein, called Cathepsin B (CatB),is a key part of a protective mechanism that may fail in some forms ofAD. Also, they said their findings suggest that drugs to enhance CatBactivity could break down amyloid deposits, counteracting one of thecentral pathologies of AD.
Li Gan and colleagues published their findings in the September 21, 2006, issue of the journal Neuron, published by Cell Press.
Theirexperiments were prompted by previous studies showing that the cysteineprotease CatB–an enzyme that snips apart proteins–closely associatedwith the amyloid-ß (Aß) protein that forms the amyloid plaques, ahallmark of AD. However, those studies had not determined whether CatBwas “good” or “bad”–that is, whether it acted to produce Aß from alonger protein, called amyloid precursor protein (APP), or whether itbroke down Aß.
In their experiments, Gan and colleaguesdetermined that CatB was the latter–breaking down Aß, apparently toenable other enzymes to further degrade the protein for the cell’sprotein “garbage deposal” system.
They found that knocking outthe CatB gene increased plaque deposition in a mouse model of AD inwhich mice expressed the human form of APP. They also found that CatBtended to accumulate within amyloid plaques and that it acted to reduceAß levels in neurons. And they found that introducing a pathologicalform of Aß, called Aß1-42, into neurons increased CatB in young andmiddle-aged mice with human APP, but not old mice. “Thus, upregulationof CatB may represent a protective mechanism that fails with aging,”wrote the researchers, and such failure may play a role in late-onsetsporadic AD.