# Targeting cell death in Crohn’s disease: from mechanisms to medicines

## TL;DR

This paper explores how different types of programmed cell death contribute to Crohn’s disease and identifies potential therapeutic strategies targeting these mechanisms.

## Contribution

The paper systematically reviews 12 cell death mechanisms in Crohn’s disease and highlights autophagy as a promising therapeutic target.

## Key findings

- Autophagy, regulated by ATGs, is crucial in Crohn’s disease and linked to genetic factors like ATG16L1 and NOD2.
- Apoptosis and pyroptosis, mediated by caspases and gasdermin, are involved in Crohn’s disease progression.
- Ferroptosis and cuproptosis are identified as potential therapeutic targets in Crohn’s disease.

## Abstract

Crohn’s disease (CD) is a chronic inflammatory granulomatous disease that can damage the gastrointestinal tract. Existing treatment methods often fail to achieve satisfactory clinical effects. Although the pathogenesis of CD has not been fully elucidated, increasing evidence suggests that programmed cell death plays a key role in disease progression. This article comprehensively reviews 12 different mechanisms of cell death related to the pathogenesis of CD: apoptosis, necroptosis, pyroptosis, parthanatos, ferroptosis, autophagy-dependent cell death, cuproptosis, oxeiptosis, entotic cell death, netotic cell death, lysosome-dependent cell death, and alkaliptosis. On this basis, the article discusses targeted therapeutic strategies to regulate these cell death pathways, with a particular emphasis on their translational potential in clinical applications. Our analysis of existing studies concludes that autophagy, regulated by ATGs, is crucial in CD, and its dysregulation is associated with genetic factors (ATG16L1, IRGM, NOD2) and the mTOR signaling pathway, suggesting that autophagy may serve as a therapeutic target. Apoptosis and pyroptosis mediated by caspases and gasdermin, respectively, as well as ferroptosis and copper death, are all involved in the pathogenesis of CD, highlighting potential therapeutic strategies through the regulation of these pathways and cell death mechanisms (Graphical abstract 1).