News from substantia nigra neuromelanin

Neuromelanin (NM) is thought to be a polymer especially of catecholaminergic neurons in the brain. NM of dopaminergic neurons of the substantia nigra pars compacta (SNpc) appears as “black“ while NM of the noradrenergic locus coeruleus (LC) shows “blue“ colour. In general, NM in the human SN is seen first at an age of 3–5 years of life and accumulates further up to an age of about 20 years. It is not synthesized in rodents. In many textbooks NM is regarded as “garbish“, a spill-over of dopamine/L-DOPA being responsible for this autoxidation product. But is it so? There are evidences to suggest that

• it does not increase continuously over life time

• it is not synthesized in all dopaminergic/noradenergic neurons.

• L-DOPA treatment of Parkinson's disease (PD) patients does not increase NM synthesis.

Therefore one might think rather NM being synthesized in specific neurons by an genetically driven mechanism. If so, such neurons would have other or additional physiological purposes compared to non-NM-catecholaminergic neurons. Such function may be:

• attenuation of effects of endogenous and endogenous neurotoxins.

• NM is the iron storing compartment of neurons

However, NM renders its neurons vulnerable for degenerating processes, possibly by inhibition of the proteasomal activity and/or by release of bound transition metals, ie iron, due to age-dependent changes in its structural composition and affinity status. An additional and important factor seems to be that the chemical structure is a complex heterologuous polymer integrating a number of proteins and lipid components. Therefore, any structural change of the core polymer will lead to changes in functional aspects expecially to binding properties as well as protein and lipid(s) function. Whether a special protein is directly or indirectly involved in the biosynthesis of NM in special granulas of SN and LC is still unknown. Nevertheless the fact that proteins are integral part of the polymer points to the view of a specific probably genetically driven mechanism of NM's synthesis. Therefore, we suggest NM to be of physiological importance in the functioning of a specific subtype of dopaminergic and noradrenergic neurons in the SN and LC respectively. NM cannot be regarded as antoxidation product and “garbish“.