I am a neurologist and neuroscientist on the
faculty at the University of Central Florida Medical School. Originally, I started this site when I
was at Dartmouth Medical School to list links that could be good teaching resources for medical students and residents
there. The main contenct still consists of the numerous categorized links to neurology, neuroscience, and other
medically related topics. Recently I have added more content in the form of news feeds and a Blog. Let me
also make the disclaimer that these are just references to information. Do not rely on what you find
here to treat yourself or anyone else. Physicians and other health care providers must use their own judgement
and multiple inputs from many sources to reach decisions. Information found here is not diagnostic or treatment
advice from me or from this web site. If you have any suggestions or comments, you may leave them in the Guestbook.----Thank
you.
In the right hand column of this page, there is an interesting item from
Medicine World.org about protecting neurons using an inhibitor of the enzyme caspace-2. This is from a paper J Biol Chem. 2011 Mar 11;286(10):8493-506. Epub 2011 Jan 7.Loss of Caspase-2-dependent Apoptosis Induces Autophagy after Mitochondrial Oxidative Stress in Primary Cultures
of Young Adult Cortical Neurons.by Tiwari M, Lopez-Cruzan M, Morgan WW, Herman B. The general gist of the explanation is reasonably clear but if you
try to go beyond the sound bite stage and actually read the little article under the headline "Potential Way to Protect
Neurons" you will encounter the confusing statement that caspase-2 protects the cell from mitochondrial stress. If so,
then why does blocking caspase-2 prolong the life of the cell?
I looked up the actual paper in the Journal of Biological
Chemistry and it is pretty clear that the statement "caspase-2 protects cells from mitochondrial stress" in the
Medicineworld article is incorrect. They probably meant to say that "inhibition of caspase-2 protects cells from mitochondrial
stress." Basically, when you treat the cells with rotenone, a pesticide, this produces oxidative mitochrondrial stress
by inhibiting complex I in the mitochondria. One way of relieving this would be to administer anti-oxidants, but that method
can only go so far in the face of total complex I shutdown. The mitochondrial stress would ordinarily start the "programmed
cell death" or apoptotic response. Caspase-2 is one of the initiators of this response. Once this program is sufficiently underway, further
enzymes are invoked and the cells dies. Blocking caspase-2 keeps apoptosis from starting. Then the cell is
free to try some other mechanisms to recover. In these experiments the cell then begins a process of "autophagy"
which means that it chews up damaged proteins (and sometimes large structures that have been damaged). This can buy time for
the cell because chewing up these proteins diverts resources to maintain the parts of the cell that are still viable. However,
in these experiments the cell is ultimately overwhelmed by the effects of mitochondrial stress and is ultimately dies anyway
via what is called "necrosis" which is a messier and less pre-programmed method of cell death in response to external
toxins such as rotenone. Enzymes are also involved to some extent, including--in some cases--the enzymes involved
in autophagy. But other experiments by other investigators have indicated that autophagy can also be involved in apoptosis.
In this case, however, the cells are blocked from performing apoptosis, autophagy is started seemingly to "try"
to recover, but ultimately the cell loses the battle and dies of necrosis. So the cells were "protected" but only
for a little while.
Just the fact that one can protect the cells even for a number of hours or days is very
important. I generally feel that once you can do something at all you can eventually find a way to increase the results. In
the human case, perhaps we can eventually buy some time while we eliminate the toxin that is causing such problems as Alzheimer's
disease or ALS.
