Cell Death

The Reverend Dr. David CM Taylor dcmt@liverpool.ac.uk

This 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 (PI-3K) pathway which promotes survival

 perhaps by preventing mitogen activated protein kinases (MAP)

 which might affect intracellular Ca2+regulation

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