Role for calcium signaling in manganese neurotoxicity

Calcium is an essential macronutrient that is involved in many cellular processes. Homeostatic control of intracellular levels of calcium ions [Ca²⁺] is vital to maintaining cellular structure and function. Several signaling molecules are involved in regulating Ca²⁺ levels in cells and perturbation of calcium signaling processes is implicated in several neurodegenerative and neurologic conditions. Manganese [Mn] is a metal which is essential for basic physiological functions. However, overexposure to Mn from environmental contamination and workplace hazards is a global concern. Mn overexposure leads to its accumulation in several human organs particularly the brain. Mn accumulation in the brain results in a manganism, a Parkinsonian-like syndrome. Additionally, Mn is a risk factor for several neurodegenerative diseases including Parkinson's disease and Alzheimer's disease. Mn neurotoxicity also affects several neurotransmitter systems including dopaminergic, cholinergic and GABAergic. The mechanisms of Mn neurotoxicity are still being elucidated.

The review will highlight a potential role for calcium signaling molecules in the mechanisms of Mn neurotoxicity.

Ca²⁺ regulation influences the neurodegenerative process and there is possible role for perturbed calcium signaling in Mn neurotoxicity. Mechanisms implicated in Mn-induced neurodegeneration include oxidative stress, generation of free radicals, and apoptosis. These are influenced by mitochondrial integrity which can be dependent on intracellular Ca²⁺ homeostasis. Nevertheless, further elucidation of the direct effects of calcium signaling dysfunction and calcium-binding proteins activities in Mn neurotoxicity is required.