Caspases are key molecules of apoptosis and the inflammatory response. Up-regulation of the caspase cascade contributes to human pathologies such as neurodegenerative and immune disorders. Thus, blocking the excessive apoptosis by pharmacological inhibitors seems promising for therapeutic interventions in such diseases. Caspase inhibitors, both natural and artificial, have been used as research tools and have helped to define the role of the individual caspases in apoptosis and in non-apoptotic processes. Moreover, some caspase inhibitors have demonstrated their therapeutic efficiency in the reduction of cell death and inflammation in animal models of human diseases. However, no drug based on caspase inhibition has been approved on the market until now. Thus, the development of therapeutic approaches that specifically target caspases remains a great challenge and is now the focus of intense biological and clinical interest. Here, we provide a brief review of recent knowledge about pharmacological caspase inhibitors with special focus on their proposed clinical applications.
- MeSH
- apoptóza účinky léků MeSH
- inhibitory kaspas farmakologie terapeutické užití MeSH
- kaspasy metabolismus MeSH
- lidé MeSH
- zánět farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Laser capture microdissection (LCM) uniquely allows the selection of specific cell populations from histological sections. These selected cells are then catapulted into a test tube without any contamination from surrounding tissues. During the last ten years, many significant results have been achieved, particularly at the level of DNA and RNA where amplification techniques are available. However, where amplification procedures are difficult, the benefits of LCM diminish. To overcome such difficulties, a novel approach, combining laser capture microdissection and flow cytometry, has been tested here for detection of apoptosis and proliferation in tissue bound cell populations without any amplification steps. The mouse cap stage molar tooth germ was used as a model. At the centre of the inner enamel epithelium, the primary enamel knot is a clearly defined apoptotic population with minimal proliferation, flanked by the highly proliferative cervical loops on each side. Thus within the tooth germ epithelium at this stage, two distinct populations of cells are found side by side. These populations were selected by laser capture microdissection and then analysed by flow cytometry for apoptosis and proliferation. Flow cytometric results correlated well with immunohistochemical findings, demonstrating the success and sensitivity of this combined procedure.
- MeSH
- apoptóza fyziologie MeSH
- epitelové buňky cytologie MeSH
- gestační stáří MeSH
- imunohistochemie MeSH
- koncové značení zlomů DNA in situ MeSH
- kryoprezervace MeSH
- laserová terapie metody MeSH
- mikrodisekce metody MeSH
- moláry embryologie MeSH
- myši MeSH
- orgán skloviny cytologie MeSH
- počet buněk MeSH
- proliferace buněk MeSH
- proliferační antigen buněčného jádra analýza MeSH
- průtoková cytometrie MeSH
- senzitivita a specificita MeSH
- zubní krček cytologie embryologie MeSH
- zubní zárodek cytologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
