Cognitive dysfunction in chemobrain: Molecular mechanisms and therapeutic implications

Area of Science:

• Neuroscience
• Oncology
• Pharmacology

Background:

• Chemotherapy-induced cognitive impairment (CICI), or chemobrain, significantly impacts cancer survivors' quality of life.
• Chemotherapeutic agents cross the blood-brain barrier, inducing neurotoxicity and cognitive dysfunction.

Purpose of the Study:

• To explore the complex molecular mechanisms underlying chemobrain.
• To discuss potential therapeutic strategies targeting key pathological pathways.

Main Methods:

• Review of existing literature on chemobrain.
• Analysis of molecular pathways including oxidative stress, mitochondrial dysfunction, NAMPT/NAD+, COX-2, and A2AR.

Main Results:

• Chemotherapy induces neurotoxicity via ROS generation, mitochondrial dysfunction, and DNA damage, impairing synaptic plasticity and neurogenesis.
• Mitochondrial dysfunction, NAMPT-dependent NAD+ depletion, COX-2 upregulation, and A2AR activation are key contributors to chemobrain.

Conclusions:

• Understanding these molecular pathways is crucial for developing effective treatments for chemobrain.
• Targeting mitochondrial dysfunction, oxidative stress, and specific molecular targets like A2AR may offer therapeutic benefits for cancer survivors experiencing cognitive impairment.