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Related Concept Videos

Stress Response System01:21

Stress Response System

206
The stress response system, also known as the fight-or-flight response, is the body's automatic physiological reaction to perceived threats. Hans Selye introduced the concept of General Adaptation Syndrome (GAS) to describe the predictable pattern of changes that occur in response to stress. GAS consists of three sequential stages: alarm, resistance, and exhaustion. This model helps explain how chronic stress can contribute to health problems.
Alarm stage
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Other Stress Responses in Bacteria01:30

Other Stress Responses in Bacteria

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Bacteria have global regulatory systems that control several types of stress mechanisms. These include Pho regulon and the heat shock response, which are essential systems for environmental adaptation, such as nutrient limitation and proteotoxic stress. The Pho regulon and the heat shock response exemplify bacterial resilience, enabling rapid adaptation to fluctuating environmental conditions.Pho RegulonBacteria require phosphorus for essential cellular processes, including nucleic acid...
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Physiological Foundation of Stress01:24

Physiological Foundation of Stress

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Stress triggers a coordinated physiological response involving the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. This dual activation ensures that the body is prepared for both immediate and prolonged stress management. The process begins with the perception of a stressor. This initial phase activates the SNS, leading to the rapid release of adrenaline (epinephrine) from the adrenal glands.
Role of the Sympathetic Nervous System
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Related Experiment Video

Updated: Sep 15, 2025

Measurements of Physiological Stress Responses in C. Elegans
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Optogenetics-enabled discovery of integrated stress response modulators.

Felix Wong1, Alicia Li1, Satotaka Omori1

  • 1Integrated Biosciences, Redwood City, CA 94065, USA.

Cell
|July 12, 2025
PubMed
Summary

Researchers developed an optogenetic platform to discover new drugs that modulate the integrated stress response (ISR). This approach identified novel compounds that enhance ISR-mediated cell death, offering therapeutic potential for various diseases.

Keywords:
antiviraldrug discoveryendoplasmic reticulum stressintegrated stress responseoptogeneticsphenotypic screeningproteostasissmall moleculessynthetic biologyunfolded protein response

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Area of Science:

  • Cellular Biology
  • Pharmacology
  • Optogenetics

Background:

  • The integrated stress response (ISR) is crucial for cellular homeostasis.
  • Modulating the ISR is therapeutically relevant for cancer, viral infections, and neurodegeneration.
  • Existing compounds often exhibit toxicity, limiting their therapeutic use.

Purpose of the Study:

  • To develop an optogenetic platform for high-throughput screening of compounds targeting the ISR.
  • To identify novel compounds that selectively modulate the ISR without cytotoxicity.
  • To explore the therapeutic potential of identified ISR modulators.

Main Methods:

  • Optogenetic clustering of PKR to induce ISR-mediated cell death.
  • High-throughput screening of 370,830 compounds.
  • Mechanistic studies involving ATF4 and GCN2.
  • In vitro and in vivo antiviral assays.

Main Results:

  • Identified compounds that potentiate ISR-mediated cell death without cytotoxicity.
  • Discovered that these compounds upregulate activating transcription factor 4 (ATF4).
  • Identified GCN2 as a molecular target and demonstrated antiviral activity, including in a mouse model.

Conclusions:

  • An optogenetic platform enables efficient drug discovery for ISR modulators.
  • Novel ISR potentiators with therapeutic potential were identified.
  • These compounds show promise for treating viral infections and other stress-related diseases.