Neuromelanin: Its role in the pathogenesis of idiopathic Parkinson's disease and potential as a therapeutic target

Parkinson's disease is an increasingly prevalent condition that involves the marked loss of dopaminergic neurons in the substantia nigra pars compacta. These neurons pigmented with neuromelanin along with other regions of the brain are almost exclusively victims of neurodegeneration in the disease. The link between neuromelanin and Parkinson's disease has been widely studied for decades. While many studies have outlined the pigment's neuroprotective function as a potent free radical scavenger, antioxidant, and ion-chelator, it has also been observed to play a role in cell death due to mitochondrial dysfunction and oxidative stress, especially in the parkinsonian disease state. This is due to the damaging effects of neuromelanin precursors, neuromelanin-related ion dysregulation and intra- and extraneuronal neuromelanin accumulation. Current and emerging therapeutic endeavours guided by these pathological processes may include antioxidant therapy, proteostasis enhancement, ion chelation and neuromelanin-targeted immunotherapy to prevent the accumulation, formation and effects of neuromelanin and oxidative neuromelanin precursors. Some of these therapeutic strategies are already in nascent stages, while others have produced mixed results in clinical trials. This review aims to provide an update on how neuromelanin and neuromelanin-related substances may be linked to the pathogenesis of Parkinson's disease and how future therapeutic strategies may be able to hamper or prevent neuromelanin-related pathological processes and ultimately modify disease progression in Parkinson's.