The Targets

Caspases, once activated, like to cut things. Things in your brain. Things you don't want cut.  Here's a partial account of the devastation:

    1. Anti-apoptotic proteins. Think about just how nasty this is. Caspases immediately attack molecules that might save the cell. We'll talk about some of these molecules later.
    2. Signaling molecules like PAK2, MEKK1, PKCdelta…you name it.
    3. ICAD. As we'll soon see, cleaving this molecule will lead to destruction of chromosomal DNA. Bad news.
    4. Calpastatin--which regulates calpain. Once again, we see how The Four Horsemen can talk to each other.
    5. DNA repair enzymes.
    6. Lamins - proteins necessary for nuclear integrity.
    7. Actin - a key component of the cytoskeleton.
    8. Fodrin (spectrin) - critical for the integrity of cellular membranes.
    9. Beta-catenin and FAK - cell adhesion molecules.
    10. Presenilins - involved in the pathogenesis of Alzheimer's.
    11. Huntington protein - involved in the pathogenesis of Huntington's Chorea.
    12. Atrophin-1 - involved in the pathogenesis of amyotrophic lateral sclerosis (Lou Gehrig's Disease).
    13. Other caspases.

If you're paying attention, you should have just done a double-take on that last item. Other caspases?

Yep. That's right. Caspases cut other caspases--and activate them. What this means is that if you activate just a little bit of the procaspase hanging out in the cell, you can initiate a caspase cascade that can expand geometrically. We'll see how this works soon.