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

Overexpression of alpha-synuclein and oxidative stress has been implicated in the neuronal cell death in Parkinson's disease. Alpha-synuclein associates with mitochondria and excessive accumulation of alpha-synuclein causes impairment of mitochondrial functions. However, the mechanism of mitochondrial impairment caused by alpha-synuclein is not fully understood. We recently reported that alpha-synuclein associates with mitochondria and that overexpression of alpha-synuclein causes nitration of mitochondrial proteins and release of cytochrome c from the mitochondria [Parihar M.S., Parihar A., Fujita M., Hashimoto M., Ghafourifar P. Mitochondrial association of alpha-synuclein causes oxidative stress. Cell Mol Life Sci. 2008a;65:1272-1284]. The present study shows that overexpression of alpha-synuclein A53T or A30P mutants or wild-type in human neuroblastoma cells augmented aggregation of alpha-synuclein. Immunoblotting and immuno-gold electron transmission microscopy show localization of alpha-synuclein aggregates within the mitochondria of overexpressing cells. Overexpressing cells show increased mitochondrial reactive oxygen species, increased protein tyrosine nitration, decreased mitochondrial transmembrane potential, and hampered cellular respiration. These findings suggest an important role for mitochondria in cellular responses to alpha-synuclein.
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PMID:Alpha-synuclein overexpression and aggregation exacerbates impairment of mitochondrial functions by augmenting oxidative stress in human neuroblastoma cells. 1946 Apr 57

The authors describe the case of a 61-year-old woman who was admitted to our intensive care unit (ICU) due to impaired consciousness associated with generalised seizures. Her cerebrospinal fluid, electrolytes, acid-base analysis, and common laboratory and toxicology tests were normal. An MRI ruled out the presence of stroke or haemorrhage but showed severe leukoencephalopathy. Parkinson's disease, Creuzfeld-Jacob disease, vascular alterations, cancer, and rheumatological and metabolic diseases were evaluated and excluded. In view of her history of hypothyroidism despite adequate hormonal replacement and clinical behaviour, Hashimoto's encephalopathy was considered. Anti-thyroperoxidase levels were above 3000 IU/ml. The patient received 5 g of methylprednisolone followed by prednisone, but after a favourable initial response, returned to a comatose state. However, after administration of intravenous immunoglobulin (IVIG) 2 g/kg, the patient recovered with resolution of neurological symptoms and was discharged from the ICU 4 days after finishing IVIG treatment.
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PMID:Successful response to intravenous immunoglobulin as rescue therapy in a patient with Hashimoto's encephalopathy. 2280 79

Mental disturbances have been described in patients with Parkinson's Disease (PD). Of these, the common conditions are delirium and psychosis. Delirium has been attributed to change of environment, especially hospital stay and infections; while psychosis is due to drugs like dopamine agonists. This is a case of a 75-year-old male, on levodopa therapy for PD, who presented with delirium and ended up with a cocktail diagnosis: Cryptococcal meningitis, Hashimoto's Encephalopathy (HE), Urinary tract infection with acute renal failure, Uremic encephalopathy and Levodopa induced psychosis. This case report, therefore, highlights the need to look for other causes of delirium in a patient with PD who is on levodopa therapy.
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PMID:Delirium in Parkinson's Disease: A Cocktail Diagnosis. 2820 16

Bacille Calmette-Guerin (BCG) vaccination is widely practiced around the world to protect against the mycobacterial infection tuberculosis. BCG is also effective against the pathogenic mycobacteria that cause leprosy and Buruli's ulcer. BCG is part of the standard of care for bladder cancer where, when given as an intravesicular irrigant, BCG acts as an immunomodulating agent and lessens the risk of recurrence. Mycobacterium avium ss. paratuberculosis (MAP) causes a fatal enteritis of ruminant animals and is the putative cause of Crohn's disease of humans. MAP has been associated with an increasingly long list of inflammatory/autoimmune diseases: Crohn's, sarcoidosis, Blau syndrome, Hashimoto's thyroiditis, autoimmune diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis, lupus and Parkinson's disease. Epidemiologic evidence points to BCG providing a "heterologous" protective effect on assorted autoimmune diseases; studies using BCG vaccination for T1D and MS have shown benefit in these diseases. This article proposes that the positive response to BCG in T1D and MS is due to a mitigating action of BCG upon MAP. Other autoimmune diseases, having a concomitant genetic risk for mycobacterial infection as well as cross-reacting antibodies against mycobacterial heat shock protein 65 (HSP65), could reasonably be considered to respond to BCG vaccination. The rare autoimmune disease, relapsing polychondritis, is one such disease and is offered as an example. Recent studies suggesting a protective role for BCG in Alzheimer's disease are also explored. BCG-induced energy shift from oxidative phosphorylation to aerobic glycolysis provides the immunomodulating boost to the immune response and also mitigates mycobacterial infection-this cellular mechanism unifies the impact of BCG on the disparate diseases of this article.
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PMID:Proposing BCG Vaccination for Mycobacterium avium ss. paratuberculosis (MAP) Associated Autoimmune Diseases. 3203 87

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