Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

2.8K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.8K
Experimental RNAi02:15

Experimental RNAi

6.9K
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.9K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

7.3K
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...
7.3K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

7.5K
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...
7.5K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

5.4K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.4K
Negative Regulator Molecules01:23

Negative Regulator Molecules

37.6K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
37.6K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Risk-adapted HLA delisting and imlifidase-enabled deceased-donor kidney transplantation in highly sensitized kidney transplant candidates: a German expert consensus report.

Frontiers in immunology·2026
Same author

A discrete time simulation model for kidney allocation in Germany.

Transplant international : official journal of the European Society for Organ Transplantation·2026
Same author

Clinical Relevance of Early Cranial Computed Tomography-Imaging After Elective Brain Tumor Surgery in Children and Adolescents.

Neurosurgery·2026
Same author

In reply: epidemiology of immune-mediated thrombotic thrombocytopenic purpura in Germany.

Research and practice in thrombosis and haemostasis·2026
Same author

APOSCREEN-1 - a prospective, single-arm clinical trial for the implementation of a pharmacy-based screening for cardiovascular-kidney-metabolic risk factors in Schleswig-Holstein.

BMC nephrology·2026
Same author

mTORC1-signaling switches megalin function from endocytosis to cell cycle progression.

Cellular and molecular life sciences : CMLS·2026
Same journal

A planar dimer of bovine ATP synthase.

Cell death and differentiation·2026
Same journal

GCN5 and TADA2B constitutively regulate XRCC1 function during DNA repair to maintain cell survival.

Cell death and differentiation·2026
Same journal

MEGF8 controls osteogenic differentiation through post-transcriptional regulation of BMP-SMAD signaling in craniosynostosis.

Cell death and differentiation·2026
Same journal

Macrophage-secreted brain-derived neurotrophic factor promotes tumor growth in triple-negative breast cancer by inducing axonogenesis.

Cell death and differentiation·2026
Same journal

Species-specific regulation of necroptosis by STK38-dependent RIPK1 phosphorylation.

Cell death and differentiation·2026
Same journal

Ssu72 phosphatase orchestrates obesogenic adipogenesis and metabolic homeostasis during nutrient excess.

Cell death and differentiation·2026
See all related articles

Related Experiment Video

Updated: Nov 27, 2025

Generation of a RIP1 Knockout U937 Cell Line Using the CRISPR-Cas9 System
08:15

Generation of a RIP1 Knockout U937 Cell Line Using the CRISPR-Cas9 System

Published on: April 11, 2025

649

Primidone blocks RIPK1-driven cell death and inflammation.

Theresa Riebeling1, Kunzah Jamal2,3, Rebecca Wilson2

  • 1Department of Nephrology and Hypertension, University Hospital Schleswig-Holstein, 24105, Kiel, Germany.

Cell Death and Differentiation
|December 4, 2020
PubMed
Summary
This summary is machine-generated.

The anti-epileptic drug primidone inhibits receptor-interacting serine/threonine protein kinase 1 (RIPK1), a key driver of inflammation and organ damage. This finding supports primidone

More Related Videos

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells
09:15

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells

Published on: October 20, 2022

2.6K
Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

13.5K

Related Experiment Videos

Last Updated: Nov 27, 2025

Generation of a RIP1 Knockout U937 Cell Line Using the CRISPR-Cas9 System
08:15

Generation of a RIP1 Knockout U937 Cell Line Using the CRISPR-Cas9 System

Published on: April 11, 2025

649
Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells
09:15

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells

Published on: October 20, 2022

2.6K
Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

13.5K

Area of Science:

  • Biochemistry
  • Pharmacology
  • Immunology

Background:

  • Receptor-interacting serine/threonine protein kinase 1 (RIPK1) is central to regulated cell death and inflammation.
  • RIPK1 inhibition offers therapeutic potential for organ damage in conditions like stroke, myocardial infarction, and kidney failure.
  • Hyperinflammation and multi-organ failure, as seen in COVID-19, involve cytokine release and RIPK1 activation.

Purpose of the Study:

  • To identify a potent RIPK1 inhibitor for treating RIPK1-dependent organ damage and hyperinflammation.
  • To evaluate the FDA-approved drug primidone as a potential RIPK1 inhibitor.

Main Methods:

  • In vitro assays to assess primidone's inhibition of RIPK1 activation.
  • A murine model of TNFα-induced shock to mimic hyperinflammatory states.
  • Detection of RIPK1 activation in respiratory tract epithelium of SARS-CoV-2 positive patients.

Main Results:

  • Primidone demonstrated potent inhibition of RIPK1 activation in vitro.
  • Primidone effectively inhibited RIPK1 activation in a murine model of TNFα-induced shock.
  • RIPK1 activation was identified in the respiratory tract epithelium of hospitalized COVID-19 patients.

Conclusions:

  • Primidone is a potent inhibitor of RIPK1 activation.
  • The findings provide a strong rationale for investigating primidone in human hyperinflammatory conditions.
  • Primidone may be a viable therapeutic option for managing RIPK1-mediated organ damage and hyperinflammation.