Neuromelanin

Neuromelanin is the name given to the complex polymer that is found in neurons in various parts of the nervous system.

"Neuromelanin... is absent at birth and becomes detectable in the brain around age one. It increases in synthesis during adolescence and continues to do so throughout a person’s lifetime. As a result, aged brains have a darker appearance in these regions. Neuromelanin is most noticeable in the substantia nigra and locus coeruleus.'(Glass, 2019)

Interestingly, humans possess uniquely high levels of NM:

"Although neuromelanin is actually present in some other species as varied as monkeys, dolphins, and frogs, the highly abundant quantity of neuromelanin in the brain stem seems unique to humans, as a dark pigmentation of this brain area is not apparently observed in other animal species at the macroscopic level. In fact, in the mammalian brain, neuromelanin accumulation increases progressively as the evolutionary relation to man becomes closer, and humans are the only species that naturally develops PD." (Vila, 2019)

Neuromelanin and Neurodegeneration

Neuromelanin has been shown to have a protective effect against neurodegenerative diseases. So let’s first discuss neurodegeneration. Neurodegenerative diseases are conditions characterised by the damage and destruction of neurons which are cells in the nervous system. Two of the most well-known and common forms of neurodegenerative disease are Alzheimer’s Disease (AD) and Parkinson's Disease (PD).

"Parkinson's disease is caused by a loss of nerve cells in part of the brain called the substantia nigra. This leads to a reduction in a chemical called dopamine in the brain. Dopamine plays a vital role in regulating the movement of the body. A reduction in dopamine is responsible for many of the symptoms of Parkinson's disease. Exactly what causes the loss of nerve cells is unclear. Most experts think that a combination of genetic and environmental factors is responsible." (NHS: Parkinson's)

“A century ago, in 1919, Konstantin Tretiakoff reported for the first time in his remarkable doctorate thesis the presence of a marked loss of pigmented neurons in the substantia nigra (SN), visible with the naked eye, in the brains of Parkinson's disease (PD) patients. Although this finding failed to gain him any significant recognition during his lifetime, his observation remains to this day the cardinal pathologic diagnostic criterion for PD.” (Vila, 2019)

Ethnicity and Neurodegeneration

Generally, the incidence of neurodegenerative conditions such as Parkinson's Disease is much higher among lighter-skinned populations than darker-skinned populations:

"Most studies report the highest prevalence of [Parkinson’s Disease] in White populations (for example 1,671.63/100,000, compared with 1,036.41/100,000 in Blacks, and 1,138.56/100,000 in Asians). Geographical location is a stronger determinant of PD risk than ethnicity. The prevalence of [Parkinson’s disease] in Black-Africans residing in sub-Saharan Africa (40/100,000) is much lower than the prevalence of [Parkinson’s Disease] amongst people of African origin living in the USA" (Ben-Joseph et al, 2020)

The fact that the rates of Parkinson’s Disease among black people in the USA and in Africa are so dramatically different shows that environmental factors clearly explain some of these disparities. But the differences between black people and white people in the US strongly suggests that there are biological and genetic factors involved too.

When I first looked into neuromelanin a few years ago, I was unaware of the complexity of the relationships between things like Parkinson’s Disease and neuromelanin. I just assumed that the lower rate of neurodegeneration among Black people must be a result of higher levels of neuromelanin in comparison to other groups. So far, I haven't yet found any studies which have directly compared levels of neuromelanin in people of different ethnicities. However, my more recent study has made me think that these ethnic disparities in neurodegenerative disease are probably more to do with the durability of neuromelanin between people of different ethnic groups rather than simply differences in quantity.

Protective effects of Neuromelanin

Parkinson’s Disease is marked by the loss of neurons which contain both dopamine and neuromelanin. What’s interesting is that while too little dopamine is associated with neurodegeneration, too much dopamine can also be problematic.

"Dopamine accumulation can induce neuronal death; however, excess dopamine can be removed by converting it into a stable compound like neuromelanin, and this process rescues the cell." (Zucca et. al, 2017)

Neuromelanin also protects neurons by binding to elements that can cause neuronal damage, in a process known as chelation.

“The ability of [neuromelanin] to act as a ‘black hole’ capable of chelating redox-active metals and a wide variety of drugs suggests that it could be a high capacity storage trapping system, and as such might prevent neuronal damage.” (Zecca et al., 2003:579)

Over-saturation of Neuromelanin in Neurons can trigger Parkinson’s

So why do these neurons die? Well, for one thing, it seems that over-concentration of neuromelanin in the substantia nigra is a risk factor for the development of Parkinson’s-like symptoms:

"The potential contribution of neuromelanin to PD pathogenesis remains unknown because, in contrast to humans, common laboratory animals lack neuromelanin. The recent introduction of a rodent model exhibiting an age-dependent production of human-like neuromelanin has allowed, for the first time, for the consequences of progressive neuromelanin accumulation—up to levels reached in elderly human brains—to be assessed in vivo. In these animals, intracellular neuromelanin accumulation above a specific threshold compromises neuronal function and triggers a PD-like pathology."(Vila, 2019)

So, although neuromelanin is a crucial player in the nervous system, and plays important protective functions for neurons, it seems that neurons might get too full of neuromelanin, and when that happens, Parkinson’s Disease symptoms ensue. The reason for this may be related to neuromelanin’s ability to bind to harmful elements:

"In neurodegenerative disorders, increases in transition metal levels have been reported... In Alzheimer’s disease (AD), the accumulation of metals is observed... and alterations in iron, copper, and zinc levels have been found in several regions of AD brain. Similarly, disturbances in metal levels have been reported in Parkinson’s disease (PD)." (Moreno-Garcia, 2021)

It has been suggested that the increased metal load might be a by-product of a loss of neuromelanin’s ability to bind to the metals. So normally, elements such as iron bind to neuromelanin and are thus prevented from causing neuronal damage. But neuromelanin may lose its ability to bind to these elements which are then released from the neuron into the brain, triggering neurodegeneration. It may also be the case that when neuromelanin reaches a saturation point, it causes the cell to die at which point, again, the neuromelanin detaches from the toxic elements which are then free to cause damage in the brain (Moreno-Garcia, 2021, Zecca et. al., 2003, Zucca et. al., 2017, Glass, 2019).

With all of this in mind, whereas before I just assumed that Black people must have more neuromelanin which explains the lower rates of neurodegenerative diseases - my thoughts have now shifted. I'm more inclined to think that the neuromelanin in Black brains is just more durable and effective, meaning that it is less prone to being saturated by toxic elements and releasing them into the Brain. There’s so much more to investigate when it comes to function of neuromelanin, so watch this space for more to come!

References

• Glass, K., 2019. Neuromelanin and Neurodegeneration. Link.

• Moreno-García, A., Kun, A., Calero, M. and Calero, O., 2021. The neuromelanin paradox and its dual role in oxidative stress and neurodegeneration. Antioxidants, 10(1), p.124. Link.

• Vila, M., 2019. Neuromelanin, aging, and neuronal vulnerability in Parkinson's disease. Movement Disorders, 34(10), pp.1440-1451. Link.

• Zecca, L., Zucca, F.A., Wilms, H. and Sulzer, D., 2003. Neuromelanin of the substantia nigra: a neuronal black hole with protective and toxic characteristics. Trends in neurosciences, 26(11), pp.578-580. Link.

• Zucca, F.A., Segura-Aguilar, J., Ferrari, E., Muñoz, P., Paris, I., Sulzer, D., Sarna, T., Casella, L. and Zecca, L., 2017. Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson's disease. Progress in neurobiology, 155, pp.96-119. Link.