Several papers report increased levels of pro-inflammatory cytokines such as tumour necrosis factor (TNF)-alpha, IL-1beta and IL-6, and decreased levels of neurotrophins such as brain-derived neurotrophic factor (BDNF) in patients with sporadic PD, with the possibility that the ability of mushroom polysaccharides to promote a shift in immune response away from a pro-inflammatory Th2 cytokine profile to a Th1 dominant state may be of benefit to patients with early stage PD1.
The tyrosinase inhibiting activity of mushrooms like Ganoderma lucidum and Flammulina velutipes may also play a role in controlling the development of PD. Tyrosinase catalyses the oxidation of tyrosine and dopamine, producing dopaquinone, which besides being the common precursor of the different forms of melanin, is a dopaminergic neuron-specific cytotoxic molecule2,3. Dopaquinone can also covalently modify and inactivate tyrosine hydroxylase, the rate limiting enzyme in catecholamine biosynthesis, leading to further reductions in levels of dopamine4.
In addition tyrosinase contributes to the formation of neuromelanin, which identifies neurons susceptible to Parkinson’s disease in cell culture systems and has been implicated in the development of the disease5.
CLINICAL NOTE
Culinary mushrooms such as F. velutipes are often preferred for long term supplementation in chronic conditions like PD.
REFERENCES
1. Inflammatory process in Parkinson’s disease: role for cytokines. Nagatsu T, Sawada M. Curr Pharm Des. 2005;11(8):999–1016.
2. Dopamine- or L-DOPA-induced neurotoxicity: the role of dopamine quinone formation and tyrosinase in a model of Parkinson’s disease. Asanuma M, Miyazaki I, Ogawa N. Neurotox Res. 2003;5(3):165–176.
3. Parkin protects against tyrosinase-mediated dopamine neurotoxicity by suppressing stress-activated protein kinase pathways. Hasegawa T, Treis A, Patenge N, Fiesel FC, Springer W, Kahle PJ. J Neurochem. 2008;105(5):1700–1715.
4. Dopamine, in the presence of tyrosinase, covalently modifies and inactivates tyrosine hydroxylase. Xu Y, Stokes AH, Roskoski R Jr, Vrana KE. J Neurosci Res. 1998;54(5):691–697.
5. Tyrosinase exacerbates dopamine toxicity but is not genetically associated with Parkinson’s disease. Greggio E, Bergantino E, Carter D, Ahmad R, Costin GE, Hearing VJ, Clarimon J, Singleton A, Eerola J, Hellström O, Tienari PJ, Miller DW, Beilina A, Bubacco L, Cookson MR. J Neurochem. 2005;93(1):246–256.