Shedding light on thyroid hormone disorders and Parkinson disease pathology: mechanisms and risk factors

Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons. Dopaminergic system is interconnected with the hypothalamic-pituitary-thyroid axis. Dopamine (DA) upregulates thyrotropin releasing hormone (TRH) while downregulating thyroid stimulating hormone (TSH) and thyroid hormones. Moreover, TRH stimulates DA release. PD is associated with impaired regulation of TSH and thyroid hormones (TH) levels, which in turn associate with severity and different subtypes of PD, while levodopa and bromocriptine treatment can interfere with hypothalamic-pituitary-thyroid axis. Thyroid disturbances, including hypothyroidism, Hashimoto's thyroiditis (HT), hyperthyroidism and Graves' disease (GD) not only increase the risk of PD but also share some clinical signs with PD. Also, several genes including RASD2, WSB1, MAPT, GIRK2, LRRK2 and gene products like neurotensin and NOX/DUOX affect the risk for both PD and thyroid disease. Hypothyroidism is associated with obesity, hypercholesterolemia, anemia and altered cerebral blood flow which are associated with PD pathology. Herein we provide a comprehensive view on the association between PD and thyroid hormones regulation and dysregulations, hoping to provide new avenues towards targeted treatment of PD. We performed a comprehensive search in literature using Pubmed and Scopus, yielding to a total number of 36 original articles that had addressed the association between thyroid hormone disorders and PD.