Related Experiment Video

Updated: May 30, 2026

Evaluation of Caspase Activation to Assess Innate Immune Cell Death
10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

The executioners sing a new song: killer caspases activate microglia

J L Venero1, M A Burguillos, P Brundin

  • 1Facultad de Farmacia, Departamento de Bioquímica y Biología Molecular, Universidad de Sevilla, Spain.

Cell Death and Differentiation
|August 13, 2011
PubMed

Insights

Executioner caspases (caspase 8 and 3/7) unexpectedly activate microglia, driving neuroinflammation in neurodegenerative diseases like Parkinson's and Alzheimer's. Inhibiting this pathway offers neuroprotection by targeting microglia.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia activation and inflammation are implicated in neurodegenerative disease pathogenesis.
  • Executioner caspases are typically associated with apoptosis but may have other roles.

Purpose of the Study:

  • To investigate the role of executioner caspases in microglia activation.
  • To explore caspase inhibition as a potential neuroprotective strategy targeting microglia.

Main Methods:

  • Analysis of caspase activation in microglia from Parkinson's disease (PD) and Alzheimer's disease (AD) subjects.
  • Inhibition of caspase signaling in cell and animal models of neurodegenerative disease.

Main Results:

  • Executioner caspases (caspase 8 and 3/7) were found to promote microglia activation independently of apoptosis.
  • These caspases are activated in microglia of PD and AD patients.
  • Inhibiting this caspase pathway reduced microglia activation and neurotoxicity in disease models.

Conclusions:

  • Microglia play a critical role in neurodegenerative disorders.
  • Executioner caspases are novel regulators of microglia activation and neuroinflammation.
  • Targeting caspases in microglia presents a promising neuroprotective therapeutic strategy.

More Related Videos

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages08:41

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages

Published on: April 6, 2022

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry05:29

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry

Published on: March 24, 2023

Related Concept Videos

Caspases01:24

Caspases

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.
The Extrinsic Apoptotic Pathway01:17

The 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...
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.
The Intrinsic Apoptotic Pathway01:31

The 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...
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.