A Comprehensive Review on CASP8: A Potential Drug Target and Biomarker

Target Name: CASP8

NCBI ID: G841

CASP8

A Comprehensive Review on CASP8: A Potential Drug Target and Biomarker

Abstract:

CASP8, short for caspase-8, is an essential enzyme in the caspase family, which plays a crucial role in cell apoptosis (programmed cell death) regulation. aberrant or dysfunctional caspases have been implicated in various diseases, including cancer, neurodegenerative diseases, and autoimmune disorders. The caspase-8 gene has been extensively studied, and several studies have identified potential drug targets and biomarkers associated with its dysfunction. In this article, we will provide a comprehensive review of CASP8, highlighting its functions, potential drug targets, and use as a biomarker for various diseases.

Introduction:

Apoptosis, a critical cell death mechanism, is essential for the development, maintenance, and regulation of tissues and organs. During apoptosis, caspases, enzymes that execute the apoptotic process, are involved in the cleavage of the lipid bilayer of the cell membrane , increasing the permeability of the cell membrane, causing changes in the internal and external environment of the cell, and ultimately leading to cell death. Among the caspases, caspase-8 (CASP8) is a key enzyme in the regulation of apoptosis.

CASP8 functions as an enzyme that activates the caspase-8-driven apoptotic cascade. It plays a crucial role in apoptosis. In the early stage of apoptosis, that is, the apoptosis induction phase (early death phase), it is responsible for identifying and cutting the lipid bilayer of the cell membrane, thereby increasing the permeability of the cell membrane, allowing apoptotic factors to enter the cell and trigger the apoptosis process..

Potential Drug Targets:

CASP8 is a protein that can be targeted by small molecules, making it an attractive drug target for various diseases. Several studies have identified potential drug targets for CASP8, including:

1. caspase-8 inhibitors: These drugs work by inhibiting the activity of caspase-8, which can prevent or reverse the execution of the apoptotic process. Potential drug targets for caspase-8 inhibitors include small molecules such as benzodiazepines and inhibitors of protein kinases, which can modulate the activity of caspase-8.

2. caspase-8 activators: These drugs work by activating the activity of caspase-8, which can enhance the execution of the apoptotic process. Potential drug targets for caspase-8 activators include small molecules such as chemoattractants and neuropeptides, which can recruit caspase-8 to its active site.

3. caspase-8 interactors: These drugs work by interacting with caspase-8, which can affect its activity. Potential drug targets for caspase-8 interactors include proteins that regulate the activity of caspase-8, such as heat shock factors (HSP70s) and transcription factors.

Biomarkers:

CASP8 dysfunction has been implicated in various diseases, including cancer, neurodegenerative diseases, and autoimmune disorders. The caspase-8 gene has been extensively studied, and several studies have identified potential biomarkers associated with its dysfunction. These biomarkers include:

1. Caspase-8 levels: The levels of caspase-8 in cells can be used as a biomarker for the expression of the CASP8 gene. Several studies have shown that decreased caspase-8 levels are associated with increased sensitivity to apoptosis, a hallmark feature of cancer.

2. Caspase-8 activity: The activity of caspase-8 can be used as a biomarker for the execution of the apoptotic process. Several studies have shown that increased caspase-8 activity is associated with increased sensitivity to

Protein Name: Caspase 8

Functions: Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic development and adulthood (By similarity). Initiator protease that induces extrinsic apoptosis by mediating cleavage and activation of effector caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death (PubMed:23516580, PubMed:8681376, PubMed:8681377, PubMed:9006941, PubMed:9184224, PubMed:8962078, PubMed:35446120, PubMed:35338844). Cleaves and activates effector caspases CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10 (PubMed:8962078, PubMed:9006941, PubMed:16916640). Binding to the adapter molecule FADD recruits it to either receptor TNFRSF6/FAS mediated or TNFRSF1A (PubMed:8681376, PubMed:8681377). The resulting aggregate called death-inducing signaling complex (DISC) performs CASP8 proteolytic activation (PubMed:9184224). The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases (PubMed:9184224). Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC (PubMed:9184224). In addition to extrinsic apoptosis, also acts as a negative regulator of necroptosis: acts by cleaving RIPK1 at 'Asp-324', which is crucial to inhibit RIPK1 kinase activity, limiting TNF-induced apoptosis, necroptosis and inflammatory response (PubMed:31827280, PubMed:31827281). Also able to initiate pyroptosis by mediating cleavage and activation of gasdermin-D (GSDMD): GSDMD cleavage promoting release of the N-terminal moiety (Gasdermin-D, N-terminal) that binds to membranes and forms pores, triggering pyroptosis (By similarity). Initiates pyroptosis following inactivation of MAP3K7/TAK1 (By similarity). Also acts as a regulator of innate immunity by mediating cleavage and inactivation of N4BP1 downstream of TLR3 or TLR4, thereby promoting cytokine production (By similarity). May participate in the Granzyme B (GZMB) cell death pathways (PubMed:8755496). Cleaves PARP1 and PARP2 (PubMed:8681376)

The "CASP8 Target / Biomarker Review Report" is a customizable review of hundreds up to thousends of related scientific research literature by AI technology, covering specific information about CASP8 comprehensively, including but not limited to:
•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
•   its importance;
•   the target screening and validation;
•   expression level;
•   disease relevance;
•   drug resistance;
•   related combination drugs;
•   pharmacochemistry experiments;
•   related patent analysis;
•   advantages and risks of development, etc.
The report is helpful for project application, drug molecule design, research progress updates, publication of research papers, patent applications, etc. If you are interested to get a full version of this report, please feel free to contact us at BD@silexon.ai

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