TRPM2: bridging calcium and ROS signaling pathways-implications for human diseases

Area of Science:

• Molecular biology
• Biophysics
• Pathophysiology

Background:

• TRPM2 is a critical ion channel involved in Ca2+ homeostasis and oxidative stress signaling.
• Dysregulation of TRPM2 is implicated in various diseases, highlighting its potential as a therapeutic target.

Purpose of the Study:

• To provide a comprehensive review of TRPM2's structural, biophysical, and signaling mechanisms.
• To explore the role of TRPM2 in neurological, cardiovascular, inflammatory, and immune system functions.
• To summarize TRPM2's involvement in cancer, including its impact on bioenergetics, oxidant defense, autophagy, and drug response.

Main Methods:

• Literature review of structural and biophysical studies on TRPM2.
• Analysis of research on TRPM2's role in various disease models.
• Synthesis of current knowledge on TRPM2 signaling pathways in cancer.

Main Results:

• TRPM2 exhibits diverse roles in cellular signaling, particularly in Ca2+ flux and response to oxidative stress.
• Context-dependent activation or inhibition of TRPM2 is necessary for therapeutic strategies.
• TRPM2 is implicated in neurodegeneration, cardiovascular dysfunction, inflammation, and immune responses.
• TRPM2 influences key cancer processes such as energy metabolism, antioxidant defense, and autophagy.

Conclusions:

• TRPM2 is a versatile therapeutic target, but its specific role requires careful consideration of the disease context.
• Further understanding of TRPM2's molecular regulation is essential for developing novel TRPM2-targeted therapies.
• TRPM2 modulation holds promise for treating a wide spectrum of diseases, including cancer.