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Watch for ICE in neurodegeneration
1Parke-Davis Pharmaceutical Research, Division of Warner-Lambert, Ann Arbor, MI 48105, USA.
Abstract:
Neuronal death occurs naturally during brain development and is a common response to an external insult. Cell death, whose mechanisms are currently being elucidated, appears in three forms: necrosis, apoptosis and programmed cell death. Recently, attention has focused on a family of cysteine proteases whose prototype is interleukin-1 beta converting enzyme (ICE). ICE, essential for IL-1 beta production and, thus, critical to necrotic mechanisms, also plays a role in apoptosis mediated through the stimulation of the lymphocyte fas antigen. The absence of ICE expression in neurons makes ICE an unlikely direct participant in neuronal death. However, the existence of ICE family members in neurons combined with the pharmacological inhibition of both apoptosis in vitro and programmed cell death during development make ICE homologs candidates for mediating these two forms of cell death. Since several neurodegenerative diseases as well as at least one neurological disorder may have an apoptotic component, antagonists of this protease family may be neuroprotective.
Insights
Neuronal death involves apoptosis and programmed cell death. ICE homologs, cysteine proteases, are potential mediators, suggesting antagonists may offer neuroprotection in neurodegenerative diseases.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Neuronal death is a natural process during development and a response to injury.
- Cell death mechanisms include necrosis, apoptosis, and programmed cell death.
- Interleukin-1 beta converting enzyme (ICE) is a key cysteine protease involved in necrosis and apoptosis.
Purpose of the Study:
- To investigate the role of ICE family members in neuronal death.
- To explore the potential of ICE antagonists as neuroprotective agents.
Main Methods:
- Review of existing literature on ICE, apoptosis, and neuronal death.
- Analysis of ICE expression and function in neuronal cells.
- Examination of pharmacological inhibition of apoptosis and programmed cell death.
Main Results:
- ICE itself is not directly expressed in neurons, making it unlikely to directly mediate neuronal death.
- ICE homologs, however, are present in neurons and may mediate apoptosis and programmed cell death.
- Pharmacological inhibition of apoptosis and programmed cell death in vitro and during development supports the role of ICE homologs.
Conclusions:
- ICE homologs are potential mediators of apoptosis and programmed cell death in neurons.
- Antagonists targeting this protease family may offer neuroprotection against neurodegenerative diseases with apoptotic components.