Neuroprotection by caspase inhibitors.
1Departments of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. johann.braun@stjude.org
Expert Opinion on Investigational Drugs
|January 5, 2001
Summary
Caspase inhibitors block apoptosis, a key driver of neuronal damage in brain diseases like Alzheimer's and epilepsy. These inhibitors show therapeutic promise for neuroprotection against various brain injuries.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Apoptosis, or programmed cell death, significantly contributes to neuronal damage in numerous brain diseases.
- Caspases are critical proteases executing the apoptotic pathway, implicating them in neurodegenerative conditions and brain injuries.
- Conditions like Alzheimer's, Huntington's disease, ALS, epilepsy, ischemia, inflammation, and trauma affect millions, with apoptosis exacerbating damage.
Purpose of the Study:
- To review recent advancements in the therapeutic application of caspase inhibitors for neuroprotection.
- To summarize current knowledge on using cell death inhibitors to mitigate neuronal damage in brain diseases.
Main Methods:
- Literature review focusing on studies investigating caspase inhibitors in neuroprotection.
- Analysis of research on the role of caspases in various neurological disorders and injury models.
Main Results:
- Caspase activity is a common pathway in diverse forms of brain damage.
- Inhibitors of caspases have demonstrated therapeutic benefits in experimental models of brain diseases.
- Targeting caspases offers a potential strategy for neuroprotection.
Conclusions:
- Inhibiting caspases represents a promising therapeutic avenue for neuroprotection across a spectrum of brain diseases.
- Further research into caspase inhibitors could lead to novel treatments for conditions involving significant neuronal loss.
Related Concept Videos
01:24Caspases
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
01:17The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
01:31The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
01:22Cellular Injury V: Apoptosis and Autophagy
Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...