Cell Death
The Reverend Dr. David CM Taylor
dcmt@liverpool.ac.ukThis page is © David Taylor and The University of Liverpool, 1999
Why do cells die?
Because they are missing some of the basic requirements for life
Or because they are told to
Basic requirements
Nutrients and O2 of course.
Cells need to be in contact with each other, and this contact is signaled chemically
So a mismatch/problem with either signal or receptor will cause problems
Apoptosis
Humans loose between 50% and 75% of the cells generated during cortical development
This is through programmed cell death or apoptosis
Genetic considerations
It is possible to breed mice with inactivated CPP32 - a gene which promotes cell death.
They have extra layers of cells in the retina and cortex
But the mice do die, because the gene is neurone specific
Regulation of apoptosis
Could account for low neuronal counts in patients with Down’s syndrome
because Bcl-2 (a cell-survival protein) is lower in post-mortem Down’s patients
while Bax (a cell-death protein)remains normal
Down’s patients generally develop Alzheimer’s disease
So...
Apoptosis seems to be a balance of cell-survival and cell-death activity
The story is quite complicated…
not least because apoptotic factors fulfil both roles
In superior cervical ganglia
BDNF acts though p75 - proapoptotic
NGF acts through Trk - antiapoptotic
NGF works through Ras to stimulate the phosphatidylinositol(3’-OH)kinase (
perhaps by preventing mitogen activated protein kinases (MAP)
which might affect intracellular Ca2+regulation