Peres, T. V., Parmalee, N. L., Martinez-Finley, E. J., and Aschner, M. (2016). Untangling the Manganese-α-Synuclein Web. Front. Neurosci. Frontiers in Neuroscience 10. doi:10.3389/fnins.2016.00364.
In this article the authors review manganese’s interaction with alpha-synuclein protein as a possible cause of dopaminergic related neurodegenerative diseases such as Parkinson’s. The hallmark of Parkinson’s is alpha-synuclein aggregation in which groups of the protein forms into tangles that cause cell death. They note that disease of excess manganese (manganism), and Parkinson’s both involve the dopaminergic systems, but in different areas of the brain.
After reviewing several studies, the authors suggest that manganese is likely only a contributing factor to alpha-synuclein aggregation. It is suggested that it interacts with other metals in the brain in a complex web to cause disease. The observation of this interaction, in various experiments cited, leads the authors to ultimately conclude that alpha-synuclein may be neuroprotective by helping to scavenge excess metals in the brain, but the protein ultimately gets overwhelmed and begins to form tangles as levels of metals rise and are unable to be cleared from the brain.
The metals that cause alpha-synuclein to tangle up and cause disease are aluminum, copper, cadmium, iron, manganese, and zinc (Paik et al., 1999). Cadmium is a well known toxic metal and should be avoided. Aluminum is present in a wide variety of products and even in food additives and serves no nutritional purpose. Thus, limiting exposure to aluminum might be a practical way to protect against neurodegenerative disease.