Melanin‐like pigment in the human prostate

Seman, G; Gallager, H. Stephen; Johnson, Douglas E.

doi:10.1002/pros.2990030109

Cited by 14 publications

(5 citation statements)

References 9 publications

(7 reference statements)

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“…Since neurons are long-lived, melanin of fungal origin could accumulate following repeated transient exposure to Malassezia . A similar mechanism could explain the presence of melanin in the basal region of prostate secretory epithelial cells, where lipid droplets are found (104).…”

Section: Malassezia and Parkinson's Diseasementioning

confidence: 87%

“…Second, the increased risk of psoriasis in overweight individuals (97–100), and the increased risk of CD in carriers of certain LRRK2 alleles (101, 102) are most simply explained by enhanced lipid availability (103) which promotes Malassezia's growth by supplying it with lipids [the same LRRK2 alleles increase PD risk (101, 102)]. Third, intracellular melanin reminiscent of neuromelanin (104) is associated with inflammation of the prostate (104–106). Though indigenous production of melanin by human cells has been proposed as an explanation (104), a second possible origin would be from Malassezia which have colonized the prostate and CNS.…”

Section: Malassezia Primermentioning

confidence: 99%

“…Third, intracellular melanin reminiscent of neuromelanin (104) is associated with inflammation of the prostate (104–106). Though indigenous production of melanin by human cells has been proposed as an explanation (104), a second possible origin would be from Malassezia which have colonized the prostate and CNS. Malassezia produce DOPA-melanin from L-DOPA (107).…”

Section: Malassezia Primermentioning

confidence: 99%

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Malassezia and Parkinson's Disease

Laurence¹,

Benito‐León

2019

Front. Neurol.

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Parkinson's disease (PD) is a common debilitating neurodegenerative disease caused by a loss of dopamine neurons in the substantia nigra within the central nervous system (CNS). The process leading to this neuronal loss is poorly understood. Seborrheic dermatitis (SD) is a common benign inflammatory condition of the skin which mainly affects lipid-rich regions of the head and trunk. SD is caused by over proliferation of the lipophilic fungus Malassezia . PD and SD are strongly associated. The increased PD risk following an SD diagnosis (OR = 1.69, 95% CI 1.36, 2.1; p < 0.001) reported by Tanner and colleagues remains unexplained. Malassezia were historically considered commensals confined to the skin. However, many recent studies report finding Malassezia in internal organs, including the CNS. This raises the possibility that Malassezia might be directly contributing to PD. Several lines of evidence support this hypothesis. AIDS is causally associated with both parkinsonism and SD, suggesting that weak T cell-mediated control of commensal microbes such as Malassezia might contribute to both. Genetic polymorphisms associated with PD ( LRRK2, GBA, PINK1, SPG11, SNCA ) increase availability of lipids within human cells, providing a suitable environment for Malassezia . Four LRRK2 polymorphisms which increase PD risk also increase Crohn's disease risk; Crohn's disease is strongly associated with an immune response against fungi, particularly Malassezia . Finally, Malassezia hypha formation and melanin synthesis are stimulated by L-DOPA, which could promote Malassezia invasiveness of dopamine neurons, and contribute to the accumulation of melanin in these neurons. Although Malassezia 's presence in the substantia nigra remains to be confirmed, if Malassezia play a role in PD etiology, antifungal drugs should be tested as a possible therapeutic intervention.

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Section: Malassezia and Parkinson's Diseasementioning

confidence: 87%

Section: Malassezia Primermentioning

confidence: 99%

Section: Malassezia Primermentioning

confidence: 99%

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Malassezia and Parkinson's Disease

Laurence¹,

Benito‐León

2019

Front. Neurol.

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“…Histological studies have found melanin inclusions within secretory epithelial cells of the prostate targeted by CD8+ T cells ( 184 – 186 ), though a fungal infection was not considered as a possible explanation. Fungi synthesize melanin as a defense mechanism when exposed to fungicides ( 187 , 188 ), so an intracellular fungus exposed to PSP94 within these cells could explain the presence of melanin.…”

Section: Links With Fungimentioning

confidence: 99%

Spondyloarthritis, Acute Anterior Uveitis, and Fungi: Updating the Catterall–King Hypothesis

Laurence¹,

Asquith

Rosenbaum

2018

Front. Med.

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Spondyloarthritis is a common type of arthritis which affects mostly adults. It consists of idiopathic chronic inflammation of the spine, joints, eyes, skin, gut, and prostate. Inflammation is often asymptomatic, especially in the gut and prostate. The HLA-B*27 allele group, which presents intracellular peptides to CD8+ T cells, is by far the strongest risk factor for spondyloarthritis. The precise mechanisms and antigens remain unknown. In 1959, Catterall and King advanced a novel hypothesis explaining the etiology of spondyloarthritis: an as-yet-unrecognized sexually acquired microbe would be causing all spondyloarthritis types, including acute anterior uveitis. Recent studies suggest an unrecognized sexually acquired fungal infection may be involved in prostate cancer and perhaps multiple sclerosis. This warrants reanalyzing the Catterall–King hypothesis based on the current literature. In the last decade, many links between spondyloarthritis and fungal infections have been found. Antibodies against the fungal cell wall component mannan are elevated in spondyloarthritis. Functional polymorphisms in genes regulating the innate immune response against fungi have been associated with spondyloarthritis (CARD9 and IL23R). Psoriasis and inflammatory bowel disease, two common comorbidities of spondyloarthritis, are both strongly associated with fungi. Evidence reviewed here lends credence to the Catterall–King hypothesis and implicates a common fungal etiology in prostate cancer, benign prostatic hyperplasia, multiple sclerosis, psoriasis, inflammatory bowel disease, and spondyloarthritis. However, the evidence available at this time is insufficient to definitely confirm this hypothesis. Future studies investigating the microbiome in relation to these conditions should screen specimens for fungi in addition to bacteria. Future clinical studies of spondyloarthritis should consider antifungals which are effective in psoriasis and multiple sclerosis, such as dimethyl fumarate and nystatin.

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“…Together, these studies suggest genital exposure to fungi may play an important etiological role in prostate disease, reactive arthritis, and MS. Could the unexplained histological evidence of fungal cells in the CNS ( 110 , 111 , 113 , 117 ) and in the prostate ( 146 , 147 ) be caused by a fungal infection spreading from the genitals after sexual debut? If so, loss of immune tolerance to this putative infection could be a plausible cause of prostate disease, reactive arthritis, uveitis, and MS.…”

Section: Genital Exposure To Fungimentioning

confidence: 99%

The Role of Fungi in the Etiology of Multiple Sclerosis

Benito‐León

Laurence²

2017

Front. Neurol.

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Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system. Infectious triggers of MS are being actively investigated. Substantial evidence supports the involvement of the Epstein-Barr virus (EBV), though other viruses, bacteria, protists, and fungi are also being considered. Many links between fungi and diseases involving chronic inflammation have been found recently. Evidence linking MS and fungi is reviewed here. The HLA-DRB1*15 allele group is the most important genetic risk factor of MS, and is a risk factor in several other conditions linked to fungal infections. Many biomarkers of MS are consistent with fungal infections, such as IL-17, chitotriosidase, and antibodies against fungi. Dimethyl fumarate (DMF), first used as an industrial fungicide, was recently repurposed to reduce MS symptoms. Its mechanisms of action in MS have not been firmly established. The low risk of MS during childhood and its moderate association with herpes simplex virus type 2 suggest genital exposure to microbes (including fungi) should be investigated as a possible trigger. Molecular and epidemiological evidence support a role for infections such as EBV in MS. Though fungal infections have not been widely studied in MS, many lines of evidence are consistent with a fungal etiology. Future microbiome and serological studies should consider fungi as a possible risk factor for MS, and future clinical studies should consider the effect of fungicides other than DMF on MS symptoms.

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Melanin‐like pigment in the human prostate

Cited by 14 publications

References 9 publications

Malassezia and Parkinson's Disease

Malassezia and Parkinson's Disease

Spondyloarthritis, Acute Anterior Uveitis, and Fungi: Updating the Catterall–King Hypothesis

The Role of Fungi in the Etiology of Multiple Sclerosis

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