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.
Highlights
Worldwide, about 20 out of 100,000 people are diagnosed with Parkinson’s disease (PD) every year [1, 2]
Could over proliferation of Malassezia in the central nervous system (CNS) contribute to PD, as it does in Seborrheic dermatitis (SD) and in immunodeficient infants undergoing lipid-rich parenteral nutrition? In this review, we explore this hypothesis in detail
Unlike sporadic PD, acquired immune deficiency syndrome (AIDS)-associated parkinsonism progresses rapidly and affects young individuals [79]. This raises the possibility that if Malassezia are present in the CNS [23, 24], their over proliferation might contribute to parkinsonism in AIDS patients, in a similar way that Malassezia on the skin contribute to SD in these patients [28, 29]
Summary
About 20 out of 100,000 people are diagnosed with Parkinson’s disease (PD) every year [1, 2]. Though immunodeficiency has been most widely studied in human immunodeficiency virus (HIV) patients [26,27,28,29,30,31,32], genetic or congenital immunological defects [33,34,35,36,37], the use of immunomodulatory drugs [38,39,40], and age-related immunosenescence [40, 41] all increase the risk of disease caused by normally well-tolerated microbes When both an overabundance of nutrients required for microbial growth and immunodeficiency occur in the same individual, this greatly favors microbial over proliferation. Could over proliferation of Malassezia in the CNS contribute to PD, as it does in SD and in immunodeficient infants undergoing lipid-rich parenteral nutrition? In this review, we explore this hypothesis in detail
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
