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:
- 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.
- Signaling molecules like
PAK2, MEKK1, PKCdelta…you name it.
- ICAD. As we'll soon
see, cleaving this molecule will lead to destruction of chromosomal DNA.
- Calpastatin--which regulates calpain. Once again, we see how The
Four Horsemen can talk to each other.
- DNA repair enzymes.
- Lamins - proteins
necessary for nuclear integrity.
- Actin - a key
component of the cytoskeleton.
- Fodrin (spectrin) -
critical for the integrity of cellular membranes.
- Beta-catenin and FAK
- cell adhesion molecules.
- Presenilins -
involved in the pathogenesis of Alzheimer's.
- Huntington protein - involved
in the pathogenesis of Huntington's Chorea.
- Atrophin-1 -
involved in the pathogenesis of amyotrophic lateral sclerosis (Lou
- 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.