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)

Abnormal involuntary movements, or dyskinesias, plague current symptomatic approaches to the treatment of Parkinson's disease. The neural mechanisms underlying the generation of dyskinesia following repeated l-3,4-dihydroxyphenylalanine (L-DOPA) or dopamine agonist administration in Parkinson's disease remain unknown. However, de novo administration of bromocriptine or lisuride to either l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned primates or patients can alleviate parkinsonian symptoms without the development of dyskinesia. In this study, we have investigated behavioral responses and alterations in the expression of opioid neuropeptide precursors preproenkephalin-A (PPE-A, encoding methionine- and leucine-enkephalin) and preproenkephalin-B (PPE-B), the precursor encoding dynorphins (dynorphin A1-17 and B1-13, leucine-enkephalin, and alpha-neoendorphin) in striatal output pathways of the 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease. Expression was assessed following repeated L-DOPA, bromocriptine, or lisuride administration. Given the functional organization of basal ganglia circuitry into anatomically discrete parallel circuits, we investigated alterations in peptide expression with reference to the detailed topography of the striatum. Following repeated L-DOPA administration (6.5 mg/kg, b.d., 21 days) in the 6-OHDA-lesioned rat a rotational response was observed. This became markedly enhanced with repeated treatment. We have previously characterized the pharmacology of this enhanced response and have suggested that it is a useful model for the elucidation of the cellular and molecular mechanisms underlying L-DOPA- and dopamine agonist-induced dyskinesia. In contrast to l-DOPA, de novo administration of bromocriptine (1 or 5 mg/kg, b.d., 21 days) or lisuride (0.01 or 0.1 mg/kg, b.d., 21 days) did not lead to an enhanced behavioral response. In vehicle-treated, 6-OHDA-lesioned animals, PPE-A expression was elevated rostrally and dorsally, while PPE-B expression was reduced in the striatum at all rostrocaudal levels. Repeated l-DOPA administration was accompanied by elevations in striatal PPE-B mRNA levels and a further elevation, above lesion-induced levels, in PPE-A expression. This further elevation was restricted to the dorsolateral striatum. However, following repeated bromocriptine or lisuride administration no increase in PPE-B expression was observed and the lesion-induced increase in PPE-A expression was normalized to prelesion levels. Increased PPE-A and PPE-B levels may, through decreasing GABA and glutamate release, respectively, in output nuclei of the basal ganglia, play a role in the development of L-DOPA- and dopamine-agonist induced dyskinesia in Parkinson's disease. These studies suggest that anti-parkinsonian treatments which are not associated with an elevation in PPE-B and/or normalize elevated PPE-A precursor expression, such as NMDA-receptor antagonists or long-acting dopamine D2 receptor agonists, e.g., cabergoline or ropinirole, may reduce dyskinesia in Parkinson's disease.
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PMID:Effect of repeated L-DOPA, bromocriptine, or lisuride administration on preproenkephalin-A and preproenkephalin-B mRNA levels in the striatum of the 6-hydroxydopamine-lesioned rat. 1007 96

While dementia is often thought of as a problem unique to the elderly patient, nearly one in ten patients with dementia is younger than 65. The etiologies of dementia in this population are varied, including a genetically inherited form of Alzheimer's disease, as well as dementia related to other problems such as Parkinson's disease, Down syndrome, and cerebrovascular disease. Health care practitioners may have difficulty diagnosing early onset dementia because the diagnostic tools and the disease manifestation differ from those of the elderly patient. In addition, treatment of early-onset dementia can also pose unique challenges related to the speed of progression of the disease, depression, and behavioral disturbances, which often plague younger patients with dementia.
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PMID:Unique problems of dementia in the younger patient. 1654 45

Occidental medicine has a given definition for Parkinson's disease and knowledge of Parkinson's disease pathophysiology has led to development of its therapeutic management. Parkinson's disease, however, is likely to have always existed in different parts of the world. Description and management of this neurodegenerative condition could be found in ancient medical systems. Here, we introduce the philosophical concepts of traditional Chinese medicine and the description, classification and understanding of parkinsonian symptoms in traditional Chinese medicine. We have conducted an in-depth review of Chinese literature reporting anti-parkinsonian and anti-dyskinetic efficacy of more than 60 traditional medicines in Parkinson's disease patients. A number of issues, however, plague the relevance of these reports and call for a scientific re-evaluation of these therapies in preclinical models of Parkinson's disease before proposing traditional Chinese medicine-based symptomatic treatment of Parkinson's disease.
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PMID:Traditional Chinese medicine for Parkinson's disease: a review of Chinese literature. 1694 Jul 61

Many of the fatal neurodegenerative disorders that plague humankind, including Alzheimer's and Parkinson's disease, are connected with the misfolding of specific proteins into a surprisingly generic fibrous conformation termed amyloid. Prior to amyloid fiber assembly, many proteins populate a common oligomeric conformation, which may be severely cytotoxic. Therapeutic innovations are desperately sought to safely reverse this aberrant protein aggregation and return proteins to normal function. Whether mammalian cells possess any such endogenous activity remains unclear. By contrast, fungi, plants and bacteria all express Hsp104, a protein-remodeling factor, which synergizes with the Hsp70 chaperone system to resolve aggregated proteins and restore their functionality. Surprisingly, amyloids can also be adaptive. In yeast, Hsp104 directly regulates the amyloidogenesis of several prion proteins, which can confer selective advantages. Here, I review the modus operandi of Hsp104 and showcase efforts to unleash Hsp104 on the protein-misfolding events connected to disparate neurodegenerative amyloidoses.
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PMID:Hsp104: a weapon to combat diverse neurodegenerative disorders. 1809 61

Stem cells hold promise to treat diseases currently unapproachable, including Parkinson's disease, liver disease and diabetes. Seminal research has demonstrated the ability of embryonic and adult stem cells to differentiate into clinically useful cell types in vitro and in vivo. More recently, the potential of fetal stem cells derived from extra-embryonic tissues has been investigated. Fetal stem cells are particularly appealing for clinical applications. The cells are readily isolated from tissues normally discarded at birth, avoiding ethical concerns that plague the isolation embryonic stem cells. Extra-embryonic tissues are large, potentially increasing the number of stem cells that can be extracted. Lastly, the generation and sequestration of cells that form extra-embryonic tissues occurs early in development and may endow resident stem cell populations with enhanced potency. In this review we summarize recent work examining the plasticity and clinical potential of fetal stem cells isolated from extra-embryonic tissues.
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PMID:Fetal stem cells from extra-embryonic tissues: do not discard. 1819 47