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Apoptosis: overview and signal transduction pathways
1Buck Institute for Age Research, Novato, California, USA. dbredesen@buckinstitute.org
Abstract:
Apoptosis is a form of cell death that is driven by an intrinsic cellular suicide program. The roles of apoptosis and other forms of programmed cell death in neural development, maintenance, and disease states are increasingly being recognized and defined. Therapies directed at the apoptotic program have seen at least some degree of success in animal models of neurodegenerative disease, vascular disease, and traumatic CNS injury. This article describes the signal transduction pathways that mediate apoptosis. Broadly speaking, intrinsic and extrinsic pathways for apoptosis activation may be distinguished, as can be cross-talk between these two. These pathways converge on a system of proteases referred to as "capases" (cysteinyl aspartic proteinases), and modulators exist that multimerize, activate, amplify, or inhibit caspases. Activated caspases are the executioners of the apoptotic program, and carry out this function by cleaving specific cellular substrates. Modulation of this process holds promise as a therapeutic approach in neurotrauma.
Insights
Apoptosis, a programmed cell death, involves intrinsic and extrinsic pathways converging on caspases. Modulating these pathways shows therapeutic promise for neurotrauma and neurodegenerative diseases.
Area of Science:
- Cell Biology
- Neuroscience
Background:
- Apoptosis is a crucial cellular suicide program.
- Its role in neural development, maintenance, and disease is increasingly recognized.
- Therapies targeting apoptosis show success in animal models of neurological disorders.
Purpose of the Study:
- To describe the signal transduction pathways mediating apoptosis.
- To highlight the convergence on caspase proteases.
- To discuss therapeutic potential in neurotrauma.
Main Methods:
- Review of intrinsic and extrinsic apoptosis pathways.
- Identification of cross-talk between pathways.
- Description of caspase activation and modulation.
Main Results:
- Apoptosis pathways converge on caspases (cysteinyl aspartic proteinases).
- Modulators regulate caspase activity (multimerization, activation, inhibition).
- Activated caspases execute apoptosis by cleaving substrates.
Conclusions:
- Understanding apoptosis pathways is key to neural development and disease.
- Caspase modulation offers a promising therapeutic strategy for neurotrauma.