Genetic and Genomic Mechanisms of Heat Stress in Disease Modulation: From Molecular Pathways to Clinical Manifestations

Dear Colleagues,

Due to the effects of global warming in recent years, the number of heatstroke cases has increased worldwide. Heatstroke is a physiological disorder in which the body is unable to properly dissipate heat, resulting in impaired thermoregulation. It progresses rapidly, causing serious water and salt imbalances and even death, underscoring its nature as an acute medical emergency.

Notably, emerging data suggest a link between heatstroke incidence and an increased risk of neurodegenerative diseases. This association points to shared molecular pathways, potentially involving genetic and epigenetic mechanisms that underlie both heat stress response and neurodegeneration.

As global warming is expected to continue for centuries, understanding the genetic and genomic basis of heat-related pathophysiology becomes increasingly urgent. It is essential to investigate how heat stress alters disease susceptibility and progression through mechanisms such as gene expression changes, genomic instability, and epigenetic modifications.

Heat stress may exacerbate diseases through the dysregulation of cellular processes, but it can also activate protective genetic pathways. For example, heat shock proteins (HSPs), which are highly conserved and regulated at the genetic level, play critical roles in maintaining proteostasis and preventing cellular damage. These responses are integral to gene–environment interactions and may modulate disease risk in a heritable manner.

Clinically, heat sensitivity is a hallmark of various conditions such as ectodermal dysplasia, and hyperthermia can trigger pathological events including febrile seizures, malignant hyperthermia, and exacerbation of neuromuscular disorders. Understanding the genetic underpinnings of these conditions in the context of heat stress may reveal novel therapeutic targets and preventive strategies.

In this Special Issue, we aim to highlight research that explores both disease-aggravating and disease-ameliorating mechanisms related to heat stress, with a particular emphasis on genetic, genomic, and molecular insights. We encourage studies that address the following:

• Genetic variants associated with heat sensitivity and thermoregulation.
• Epigenetic alterations induced by heat stress.
• Gene expression profiling in heat-related illnesses.
• Genomic and transcriptomic mechanisms of heat shock proteins and other stress responders.
• The role of non-coding RNAs in heat response pathways.
• Population genetics aspects of heat adaptation.
• Model organism studies revealing conserved genetic pathways of thermotolerance.
• Clinical genetics of heat-sensitive disorders (e.g., ectodermal dysplasia, febrile seizures, malignant hyperthermia).

We welcome original research, reviews, and methodological papers that contribute to a genetic and genomic understanding of heat stress and its role in modulating disease. Submissions that integrate multi-omics approaches (e.g., genomics, transcriptomics, epigenomics) are especially encouraged.

Dr. Hisahide Nishio
Prof. Dr. Hiroyuki Awano
Guest Editors

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• heatstroke
• global warming
• heat stress
• neurodegenerative diseases
• molecular pathogenesis
• gene–environment interactions