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. 2023 Sep 29:14:1228530.
doi: 10.3389/fimmu.2023.1228530. eCollection 2023.

Melanin: a unifying theory of disease as exemplified by Parkinson's, Alzheimer's, and Lewy body dementia

Stacie Z Berg  1 , Jonathan Berg  1
Affiliations

Melanin: a unifying theory of disease as exemplified by Parkinson's, Alzheimer's, and Lewy body dementia

Stacie Z Berg et al. Front Immunol. .

Abstract

Melanin, a ubiquitous dark pigment, plays important roles in the immune system, including scavenging reactive oxygen species formed in response to ultraviolet radiation absorption, absorbing metals, thermal regulation, drug uptake, innate immune system functions, redox, and energy transduction. Many tissue types, including brain, heart, arteries, ovaries, and others, contain melanin. Almost all cells contain precursors to melanin. A growing number of diseases in which there is a loss of melanin and/or neuromelanin are increasingly thought to have infectious etiologies, for example, Alzheimer's disease (AD), Parkinson's disease (PD), Lewy Body Dementia (LBD), and vitiligo. AD, PD, LBD, and vitiligo have been linked with herpesvirus, which enters melanosomes and causes apoptosis, and with gut dysbiosis and inflammation. Herpesvirus is also linked with gut dysbiosis and inflammation. We theorize that under normal healthy states, melanin retains some of the energy it absorbs from electromagnetic radiation, which is then used to fuel cells, and energy from ATP is used to compliment that energy supply. We further theorize that loss of melanin reduces the energy supply of cells, which in the case of AD, PD, and LBD results in an inability to sustain immune system defenses and remove the plaques associated with the disease, which appear to be part of the immune system's attempt to eradicate the pathogens seen in these neurodegenerative diseases. In addition, in an attempt to explain why removing these plaques does not result in improvements in cognition and mood and why cognitions and moods in these individuals have ebbs and flows, we postulate that it is not the plaques that cause the cognitive symptoms but, rather, inflammation in the brain resulting from the immune system's response to pathogens. Our theory that energy retained in melanin fuels cells in an inverse relationship with ATP is supported by studies showing alterations in ATP production in relationship to melanin levels in melanomas, vitiligo, and healthy cells. Therefore, alteration of melanin levels may be at the core of many diseases. We propose regulating melanin levels may offer new avenues for treatment development.

Keywords: Alzheimer’s disease; Lewy body dementia; Parkinson’s disease; amyloid plaque; glyphosate; gut microbiome; inflammation; melanin.

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Conflict of interest statement

Authors SB and JB were employed by the company William Edwards LLC.

Figures

Figure 1
Figure 1
Viral-related neural inflammation and neurodegeneration. Infection with a microbe (for example, HSV) triggers an immune response, which leads to the formation of an encapsulating plaque (Aß) and inflammation, while reducing melanin levels through apoptosis and/or usurpation by pathogens. The loss of melanin triggers mitochondrial dysfunction, which leads to increased ROS, which triggers an immune response, which triggers inflammation. Low melanin levels/apoptosis also cause hearing/smell loss, vision problems, and drug hypersensitivity. Loss of melanin also may be seen in the skin (not shown). The pathogen also triggers the release of mast cells in an immune response (not shown). Mast cells degranulate and release histamine and other immune system inflammatory chemicals. The immune response to both the pathogen and reduced melanin levels lead to inflammation, and the pathogen triggers apoptosis, which reduces melanin and dopamine (not shown), all of which lead to dementia and other neurodegenerative disease symptoms.
Figure 2
Figure 2
We theorize there is an inverse relationship between melanin levels and ATP production. (A) Small molecule inhibitors of mtATPase, which inhibit mitochondrial ATP production, increase melanin production by a factor of three-fold or greater in melan-p1 cells. Therefore, melanin levels rise when the ATP pathway is blocked. Light-emitting equipment increases levels of cellular ATP, we theorize, because not as much ATP is being used as a result of increased availability of melanin/neuromelanin. Light is not a precursor to ATP production; however, light is a precursor to melanogenesis. Therefore, we conjecture that when pigmented cells were exposed to the emitted light, they produced melanin/neuromelanin. Hence, it appears ATP levels rise when cells that produce melanin/neuromelanin are exposed to light. This suggests that ATP production and melanin production are inversely related. (B) Upregulating the production of Mitofusin-2 increases ATP production, while decreasing the rate of melanogenesis, and downregulation of the production of Mitofusin-2 decreases ATP production, while increasing the rate of melanogenesis. (C) Prohibitin is a protein found in the mitochondria, nucleus, cell membrane, and cytosol and shuttles amongst them. We theorize prohibitin is communicating energy needs among these cellular components to produce ATP and balancing that with its known roles of mitochondrial biogenesis and melanogenesis, the latter of which we theorize is providing the primary energy to cells.
Figure 3
Figure 3
Melanin has the ability to conduct, store, and release energy. Melanin: The unifying theory of disease describes a new understanding of the role of melanin as a primary energy supplier to cells, with an inverse relationship with ATP production, and provides a new theory on the pathology of neurodegenerative and other diseases. We propose that in neurodegenerative disease, the loss of melanin/neuromelanin reduces cellular energy in the brain, which interferes with the immune system’s ability to clear the plaques encapsulating microbes that may have migrated from the gut via the vagus nerve, nose via the olfactory nerve, or via some other pathway. The loss of melanin also can lead to disruption of electrical impulses that can result in cardiac arrhythmias and seizures. Excessive melanogenesis can fuel diseases, such as melanoma.
Figure 4
Figure 4
Raper-Mason melanogenesis pathway. Eumelanin, pheomelanin, and neuromelanin involve L-DOPA. L-DOPA is a precursor to dopamine. Dopamine plays a major role in PD, LBD, and AD.
See this image and copyright information in PMC

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