Related Experiment Video
Updated: Jun 5, 2026
Two-vessel Occlusion Mouse Model of Cerebral Ischemia-reperfusion
Published on: March 1, 2019
Fas/CD95 regulatory protein Faim2 is neuroprotective after transient brain ischemia
Arno Reich1, Christopher Spering, Karen Gertz
1Department of Neurology, University Hospital and Medical School, RWTH Aachen University, D-52074 Aachen, Germany.
Abstract:
Death receptor (DR) signaling has a major impact on the outcome of numerous neurological diseases, including ischemic stroke. DRs mediate not only cell death signals, but also proinflammatory responses and cell proliferation. Identification of regulatory proteins that control the switch between apoptotic and alternative DR signaling opens new therapeutic opportunities. Fas apoptotic inhibitory molecule 2 (Faim2) is an evolutionary conserved, neuron-specific inhibitor of Fas/CD95-mediated apoptosis. To investigate its role during development and in disease models, we generated Faim2-deficient mice. The ubiquitous null mutation displayed a viable and fertile phenotype without overt deficiencies. However, lack of Faim2 caused an increase in susceptibility to combined oxygen-glucose deprivation in primary neurons in vitro as well as in caspase-associated cell death, stroke volume, and neurological impairment after cerebral ischemia in vivo. These processes were rescued by lentiviral Faim2 gene transfer. In summary, we provide evidence that Faim2 is a novel neuroprotective molecule in the context of cerebral ischemia.
Insights
Fas apoptotic inhibitory molecule 2 (Faim2) protects neurons from ischemic stroke. Loss of Faim2 increased stroke severity, but gene therapy restored protection, highlighting Faim2 as a novel neuroprotective target.
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- Death receptor (DR) signaling influences neurological diseases like ischemic stroke.
- DRs regulate apoptosis, inflammation, and cell proliferation.
- Identifying DR signaling regulators offers therapeutic potential.
Purpose of the Study:
- To investigate the role of Fas apoptotic inhibitory molecule 2 (Faim2) in neurological disease models.
- To determine if Faim2 acts as a neuroprotective agent against cerebral ischemia.
Main Methods:
- Generated Faim2-deficient mice to study its function.
- Utilized in vitro oxygen-glucose deprivation in primary neurons.
- Assessed in vivo cerebral ischemia models and employed lentiviral Faim2 gene transfer for rescue experiments.
Main Results:
- Faim2 deficiency increased neuronal susceptibility to oxygen-glucose deprivation in vitro.
- Lack of Faim2 exacerbated caspase-associated cell death, stroke volume, and neurological deficits in vivo.
- Lentiviral Faim2 gene transfer successfully rescued these detrimental effects.
Conclusions:
- Faim2 is a neuron-specific inhibitor of apoptosis.
- Faim2 demonstrates significant neuroprotective effects against cerebral ischemia.
- Faim2 represents a novel therapeutic target for treating ischemic stroke.
Related Concept Videos
01:15Ischemic Stroke ll: Pathophysiology
01:26Transient Ischemic Attack l: Introduction
01:15Ischemic Stroke l: Introduction