Untangling the Manganese-α-Synuclein Web

Neurodegenerative diseases affect a significant portion of the aging population. Several lines of evidence suggest a positive association between environmental exposures, which are common and cumulative in a lifetime, and development of neurodegenerative diseases. Environmental or occupational exposure to manganese (Mn) has been implicated in neurodegeneration due to its ability to induce mitochondria' dysfunction, oxidative stress, and alpha-synuclein (alpha-Syn) aggregation. The role of the alpha-Syn protein visa-vis Mn is controversial, as it seemingly plays a duplicitous role in neuroprotection and neurodegeneration. alpha-Syn has low affinity for Mn, however an indirect interaction cannot be ruled out. In this review we will examine the current knowledge surrounding the interaction of alpha-Syn and Mn in neurodegenerative process.