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Apoptosis in neural development and disease
  1. Nicholas D Mazarakis,
  2. A David Edwards,
  3. Huseyin Mehmet
  1. Neonatal Neurosciences Unit, Division of Paediatrics and Gynaecology, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Rd, London W12 ONN
  1. Dr Huseyin Mehmet. Email:hmehmet{at}rpms.ac.uk

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Neural cell death has a pivotal role in both the development and pathophysiology of the nervous system. Two distinct modes of cell death—necrosis and apoptosis—are involved in pathological neuronal loss, but apoptosis alone is the mechanism of programmed cell death during development. All cells will undergo apoptosis in the absence of survival signals, usually peptide growth factors secreted by other cells. This provides an elegant mechanism for the control of neuronal development: a surplus of neurons is produced, and only those that form the correct connections with the target tissue receive adequate survival factors. The remainder undergo apoptotic death and removal. Apoptosis continues throughout life and is the central mechanism for the removal of surplus, unwanted, damaged or aged cells. Dysregulation of apoptosis is seen after cellular insults or in neurodegeneration as well as in tumourigenesis. Strategies which influence the apoptotic pathway offer valuable therapeutic approaches in a variety of pathological states.

Apoptosis

The term programmed cell death was first used by Lockshin and Williams in 1964, to describe the pre-determined loss of specific cells during insect metamorphosis by an intrinsic cellular suicide programme.1 In a seminal paper Kerr, Wyllie, and Currie2 later coined the word apoptosis to describe this form of death and went on to show that it was a widespread process in nature, occurring both during normal physiological development and in many pathological conditions.

Apoptosis is a well conserved and highly regulated mechanism of cell death for the removal of unnecessary, surplus, aged or damaged cells. Dysregulation of apoptosis can result in the persistence of mutated cells, leading to malformations, autoimmune disease, and cancer. On the other hand, inappropriate apoptosis resulting in the removal of healthy cells can occur in diseases such as infection, hypoxic–ischaemic injury, neurodegenerative or neuromuscular diseases, and AIDS.

Apoptosis can be distinguished …

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