Role of Activating Transcription Factor 4 in Metabolic, Neurologic, and Ocular Diseases

TL;DR

This paper reviews how the protein ATF4 helps cells handle stress but can also cause diseases like metabolic disorders, neurological issues, and eye problems.

Contribution

The paper synthesizes ATF4's dual role in disease and protection, offering insights into its context-dependent effects and therapeutic potential.

Findings

ATF4 activation can both protect cells and induce apoptosis under stress.

ATF4 is involved in metabolic dysfunction, neurodegenerative diseases, and ocular pathologies.

The study highlights ATF4's potential as a therapeutic target across multiple disease types.

Abstract

Cells respond to metabolic and environmental challenges through the integrated stress response (ISR), a cellular process that maintains homeostasis under diverse stressors. ATF4 is a key player in this ISR, as it is activated via the PERK–eIF2α–ATF4 pathway. ATF4 induction can elicit adaptive responses, including the regulation of genes involved in metabolism and autophagy, to maintain homeostasis. However, ATF4 activation can also induce apoptosis, leading to a wide spectrum of diseases, including metabolic, neurologic, and ocular pathologies. This duality reflects the highly context-dependent nature of ATF4 signaling. This review aims to synthesize the role of ATF4 in metabolic dysfunction, neurodegenerative diseases, and ocular pathology; the mechanisms underlying its protective versus pathologic effects; and future directions to refine ATF4’s potential as a clinical therapeutic target across different diseases.

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