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Neuronal cell death: when, why and how
1Eisai London Research Laboratories Ltd, University College London, UK.
Abstract:
Apoptosis is recognised increasingly as a prominent event in nervous system development and disease. This form of death appears to obey the same rules in neurones as in other cells, in that it is initiated by similar extracellular perturbations and distinguished by similar morphological and biochemical changes. When neurones die after survival factor withdrawal, gene transcription is important, with the transcription factor c-jun and the cytoplasmic signalling cascade that regulates it being particularly significant in at least some types of cells. However, death can be induced in a transcription-independent manner by agents such as staurosporine. Both types of death involve activation of members of the ICE family of proteases but, surprisingly, the particular protease involved seems to depend very much on the manner in which death is initiated.
Insights
Neuronal apoptosis, or programmed cell death, in the nervous system follows similar rules to other cells. The specific proteases activated during neuronal apoptosis depend on how the cell death process is initiated.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Apoptosis is increasingly recognized as a key process in nervous system development and disease.
- Neuronal apoptosis shares morphological and biochemical similarities with apoptosis in other cell types.
- Cell death can be triggered by various extracellular factors and internal signaling pathways.
Purpose of the Study:
- To investigate the mechanisms of apoptosis in neurons.
- To understand the role of gene transcription in neuronal cell death.
- To identify the specific proteases involved in different modes of neuronal apoptosis.
Main Methods:
- Investigated neuronal apoptosis triggered by survival factor withdrawal.
- Examined transcription-independent neuronal death induced by agents like staurosporine.
- Analyzed the activation of ICE family proteases in response to different death stimuli.
Main Results:
- Gene transcription, particularly involving the c-jun transcription factor, is crucial for neuronal death upon survival factor withdrawal.
- Neuronal death can also occur independently of gene transcription, as demonstrated with staurosporine.
- Activation of ICE family proteases is common to both transcription-dependent and -independent neuronal apoptosis.
- The specific ICE family protease activated differs depending on the mode of apoptosis initiation.
Conclusions:
- Neuronal apoptosis is a regulated process influenced by both transcriptional and non-transcriptional pathways.
- The choice of ICE family protease in neuronal apoptosis is contingent on the initiating stimulus.
- Understanding these pathways is vital for addressing nervous system development and disease.