Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An association between arteriosclerosis and homocysteine (Hcy) was first demonstrated in 1969. Hcy is a sulfur containing amino acid derived from the essential amino acid methionine (Met). Hyperhomocysteinemia (HHcy) was subsequently shown in several age-related pathologies such as osteoporosis, Alzheimer's disease, Parkinson's disease, stroke, and cardiovascular disease (CVD). Also, Hcy is associated with (but not limited to) cancer, aortic aneurysm, hypothyroidism and end renal stage disease to mention some. The circulating levels of Hcy can be increased by defects in enzymes of the metabolism of Met, deficiencies of vitamins B6, B12 and folate or by feeding Met enriched diets. Additionally, some of the pharmaceuticals currently in clinical practice such as lipid lowering, and anti-Parkinsonian drugs are known to elevate Hcy levels. Studies on supplementation with folate, vitamins B6 and B12 have shown reduction in Hcy levels but concomitant reduction in certain associated pathologies have not been definitive. The enormous importance of Hcy in health and disease is illustrated by its prevalence in the medical literature (e.g. > 22,000 publications). Although there are compelling data in favor of Hcy as a modifiable risk factor, the debate regarding the significance of Hcy mediated health effects is still ongoing. Despite associations between increased levels of Hcy with several pathologies being well documented, whether it is a causative factor, or an effect remains inconclusive. The present review though not exhaustive, is focused on several important aspects of Hcy metabolism and their relevance to health.
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PMID:The metabolism and significance of homocysteine in nutrition and health. 2929 40

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.
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PMID:Shedding light on thyroid hormone disorders and Parkinson disease pathology: mechanisms and risk factors. 3250 Apr 45


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