Neuroprotection in Oxidative Stress-Related Neurodegenerative Diseases: Role of Endocannabinoid System Modulation.

SIGNIFICANCE: Redox imbalance may lead to overproduction of reactive oxygen and nitrogen species (ROS/RNS) and subsequent oxidative tissue damage, which is a critical event in the course of neurodegenerative diseases. It is still not fully elucidated, however, whether oxidative stress is the primary trigger or a consequence in the process of neurodegeneration. Recent Advances: Increasing evidence suggests that oxidative stress is involved in the propagation of neuronal injury and consequent inflammatory response, which in concert promote development of pathological alterations characteristic of most common neurodegenerative diseases. CRITICAL ISSUES: Accumulating recent evidence also suggests that there is an important interplay between the lipid endocannabinoid system [ECS; comprising the main cannabinoid 1 and 2 receptors (CB1 and CB2), endocannabinoids, and their synthetic and metabolizing enzymes] and various key inflammatory and redox-dependent processes. FUTURE DIRECTIONS: Targeting the ECS to modulate redox state-dependent cell death and to decrease consequent or preceding inflammatory response holds therapeutic potential in a multitude of oxidative stress-related acute or chronic neurodegenerative disorders from stroke and traumatic brain injury to Alzheimer's and Parkinson's diseases and multiple sclerosis, just to name a few, which will be discussed in this overview. Antioxid. Redox Signal. 29, 75-108.