Manganese is a heavy metal, but humans will be easily exposed to its high levels from the environment, including some pesticides and mines. If humans are exposed to high levels of manganese chronically, it can cause neurotoxicity, exhibiting Parkinson’s disease-like symptoms. But we do not know the toxicity mechanisms associated with its toxicity, and thus, no effective treatment is available. We are studying the toxicity mechanisms as well as the protection mechanisms. We test several genes, YY1, REST, and LRRK2, to determine if they are involved in manganese toxicity mechanisms. We also tested whether estrogenic compounds, such as tamoxifen, which induce neuroprotection in neurodegenerative diseases, can protect against manganese toxicity and the potential mechanism involved. This can lead to the development of estrogenic compounds, which specifically act on the brain without exerting side effects in the other parts of the body.