Is a hypothetical melanoma-like neuromelanin the underlying factor essential for the aetiopathogenesis and clinical manifestations of multiple sclerosis?

Abstract

BackgroundMultiple sclerosis (MS) has undergone a significant increase in incidence in the industrialised nations over the last 130 years. Changing environmental factors, possibly infections or a lack of or altered timing of them, determine the prevalence of the disease. Although a plethora of aetiological factors, clearly evident in a group of children with MS, appear relevant, there may nevertheless be a single factor essential for the aetiopathogenesis and clinical manifestation of MS.Description and discussionThis hitherto unknown factor is postulated to be a ‘melanoma-like neuromelanin’ (MLN) dependent on the activation of a gene for syncytin-1. An involvement of MLN could explain the diverse findings in the epidemiology, immunology and pathology of MS, requiring a consideration of a complex infectious background, the human leucocyte antigens, as well as cosmic radiation causing geomagnetic disturbances, vitamin D deficiency, smoking, and lower levels of uric acid.SummaryIn principle, the MLN-based concept is a unifying one, capable of explaining a number of characteristics of the disease. To date, MLN has not been addressed in studies on MS and future work will need to be done on human patients, as there is little or no neuromelanin (the precursor of MLN) in the animals used as experimental models in the study of MS.

The Relationship between Geomagnetic Disturbances and Multiple Sclerosis at the Edge of the Auroral Zone

“…Depending on the amount or location of damage to MBP or other proteins within the myelin sheath, MS cases might be mild or quite severe such as the Marburg variant. Krone and Granger's review of the literature [50] suggests that GMDs and other cosmic radiation may alter ironcontaining melanoma-like neuromelanin which, in turn, may promote demyelination in MS patients. Further studies of these relationships are necessary to explore GMDs as a possible risk factor for MS and to clarify possible mechanisms.…”

The Why of Sporadic Motor Neuron Disease - Many Factors, still a Mystery?

“…Most likely inflammation of any origin is contributing, presumably by generation of longer living reactive oxygen species such as hydrogen peroxide. Iron ions stored in the melanin can use it in the Fenton reaction to produce the very short living highly reactive hydroxyl radical 6 and subsequently might modify BC, that are stored at the same place, to neurotoxins, structurally similar to the experimentally used Parkinson toxin (precursor) methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine. Members of the large family of BC exhibit a broad spectrum of biological activities and can affect multiple central nervous system targets including a modulation of the activity of glutamate transporters via gene activation 11 .…”

“…have been described as a risk factor 1,2 . Natural neuromelanin has also paramagnetic properties due to its content of iron 6 and might account for a vulnerability to electric shock and eventually even to extremely low-frequency electromagnetic fields 1,2 . A quantitative reduction of neuromelanin could be helpful as is a feature of Parkinson's.…”

“…Unfortunately anti-retroviral therapy proved helpful only with exogenous viruses, not in the frequent cases with expression of HERVs 4 . We previously suggested a role for HERVs in melanoma and in multiple sclerosis via an altered biosynthesis of melanin of the skin and, though hypothetical, of neuromelanin, respectively 5,6 . Melanins incorporate metal ions and toxicants 6 .…”

“…We previously suggested a role for HERVs in melanoma and in multiple sclerosis via an altered biosynthesis of melanin of the skin and, though hypothetical, of neuromelanin, respectively 5,6 . Melanins incorporate metal ions and toxicants 6 . Could it be that a hypothetical altered neuromelanin with increased storage capacity, in particular in the locus coeruleus, is of key-importance in SMND?…”