Malassezia and Parkinson's Disease

Abstract

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.

Malassezia-Associated Skin Diseases, the Use of Diagnostics and Treatment

“…These include those with Parkinson's disease (Skorvanek and Bhatia, 2017) patients as well as patients with spinal cord injury on which seborrheic dermatitis appears above the level of injury (Han et al, 2015), pointing toward brain-skin axis involvement. In the light of the recent implication of Malassezia yeasts in pancreatic ductal carcinoma development (Aykut et al, 2019), these epidemiological observations point to future research areas (Laurence et al, 2019). The understanding of the pathogenesis of seborrheic dermatitis is limited by the overlap with other conditions such as psoriasis (sebopsoriasis), the indistinct borders between seborrheic dermatitis and dandruff and the absence of a robust severity scoring system.…”

Bacterial, viral, and fungal infection‐related risk of Parkinson's disease: Meta‐analysis of cohort and case–control studies

“…In our meta-analysis, Malassezia infection was related to increased risk of PD (Laurence et al, 2019). Recent studies have shown that PD is associated with seborrheic dermatitis (Laurence et al, 2019), which is known to affect approximately 52%-59% PD patients, and is caused by the excessive proliferation of the lipophilic fungus Malassezia (Laurence et al, 2019). Interestingly, Malassezia has been identified in central nervous system, indicating a possibility that Malassezia may directly contribute to PD (Laurence et al, 2019).…”

“…Infection of various pathogenic microorganisms has been thought associated with increased risk of PD, including Helicobacter pylori (HP; Shen, Yang, Wu, Zhang, & Jiang, 2017), hepatitis C virus (HCV; Wijarnpreecha, Chesdachai, Jaruvongvanich, & Ungprasert, 2018), Malassezia (Laurence, Benito-León, & Calon, 2019), Chlamydophila pneumoniae (C. pneumonia; Bu et al, 2015), hepatitis B virus (HBV; Wijarnpreecha et al, 2018), influenza virus (Vlajinac et al, 2013), measles (Vlajinac et al, 2013), varicella-zoster virus (VZV; Hemling et al, 2003), mumps (Vlajinac et al, 2013), German measles (Vlajinac et al, 2013), pertussis (Vlajinac et al, 2013), scarlet fever (Vlajinac et al, 2013), rheumatic fever (Vlajinac et al, 2013), diphtheria (Vlajinac et al, 2013), cytomegalovirus (CMV; Bu et al, 2015), Epstein-Barr virus (EBV; Bu et al, 2015), herpes virus (HSV; Hemling et al, 2003), and Borrelia burgdorferi (B. burgdorferi; Bu et al, 2015). However, there are also studies indicated that infection of these pathogenic microorganisms may decrease or does not affect the risk of PD (Harris, Tsui, Marion, Shen, & Teschke, 2012).…”

Parkinson's Disease: A Comprehensive Analysis of Fungi and Bacteria in Brain Tissue

“…Also, the possibility that some toxins or fungi can provoke PD has been suggested [30][31][32][33][34]. More recently, the possibility that Malassezia might be contributing to PD has been hypothesized [35]. However, the direct demonstration that these pathogens are present in brain tissue of PD patients was not provided.…”