Role of manganese in brain health and disease: Focus on oxidative stress

Area of Science:

• Environmental Toxicology
• Neuroscience
• Cellular Biology

Background:

• Manganese (Mn) is an essential trace element vital for physiological functions.
• Excessive manganese exposure poses significant health risks, notably neurotoxicity.
• Manganese-induced oxidative stress is a key factor in cellular dysfunction and disease.

Purpose of the Study:

• To synthesize current knowledge on manganese-induced oxidative stress and its role in cellular dysfunction.
• To elucidate the mechanisms by which manganese promotes toxicity.
• To identify and evaluate potential therapeutic compounds for manganese toxicity.

Main Methods:

• Literature review of current research on manganese toxicity.
• Analysis of cellular pathways affected by manganese exposure.
• Examination of therapeutic interventions and their mechanisms of action.

Main Results:

• Manganese promotes toxicity primarily through reactive oxygen species (ROS) generation, leading to oxidative stress.
• Key affected pathways include mitochondrial dysfunction, endoplasmic reticulum stress, inflammasome activation, and epigenetic modifications.
• Several compounds (e.g., probucol, metformin, curcumin, resveratrol, daidzein) show protective effects via antioxidant and mitochondrial support.

Conclusions:

• Manganese toxicity involves complex cellular disruptions driven by oxidative stress.
• Identified therapeutic compounds offer promising strategies for mitigating manganese-induced disorders.
• Further research is needed for targeted therapies and combination approaches to combat manganese toxicity.