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)

The association between suicide and medical disorder has not received as much attention as the association between suicide and psychiatric disorder. We identified by statistical overview medical disorders with an altered suicide risk. We found reports on the mortality of 63 medical disorders (ICD9 001-289, 320-999) said to have an altered suicide risk. English-language reports were located on MEDLINE with the search terms "disease name with mortality and follow-up"; and from the reference lists of these reports. We abstracted 235 reports of mortality studies of medical disorders with 2 years or more of follow-up, less than 10% loss of subjects, observed numbers of suicides given, and either the expected number or the facts from which to derive this. The ratio of the sum of the observed to the sum of the expected suicides, for each disorder, tested by the Poisson distribution gave an assessment of altered risk of death from suicide. Increased risk (p < 0.05) was seen for HIV/AIDS, malignant neoplasms as a group, head and neck cancers, Huntington disease, multiple sclerosis, peptic ulcer, renal disease, spinal cord injury, and systemic lupus erythematosus. Inconclusive evidence for increased risk was observed for amputation, heart valve replacement and surgery, disorders of the intestine (Crohn disease, ileostomy, ulcerative colitis), hormone replacement therapy, alcoholic liver disease, neurofibromatosis, systemic sclerosis, and Parkinson disease. Pregnancy and the puerperium had decreased risks (p < 0.05). There was no evidence of either increased or decreased risk for any of the other disorders studied.
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PMID:Suicide as an outcome for medical disorders. 798 80

A number of neurological disorders can manifest as isolated pain or as joint, muscle or bone alterations. These manifestations can raise significant diagnostic challenges when they occur early, before the development of neurological and/or radiological abnormalities. This chapter discusses neuropathic osteoarthropathies, neurofibromatosis, Parkinson's disease, multiple sclerosis and the complications of central nervous system lesions.
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PMID:Musculoskeletal problems of neurogenic origin. 1092 48

Drosophila melanogaster has been utilized to model human brain diseases. In most of these invertebrate transgenic models, some aspects of human disease are reproduced. Although investigation of rodent models has been of significant impact, invertebrate models offer a wide variety of experimental tools that can potentially address some of the outstanding questions underlying neurological disease. This review considers what has been gleaned from invertebrate models of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, metabolic diseases such as Leigh disease, Niemann-Pick disease and ceroid lipofuscinoses, tumor syndromes such as neurofibromatosis and tuberous sclerosis, epilepsy as well as CNS injury. It is to be expected that genetic tools in Drosophila will reveal new pathways and interactions, which hopefully will result in molecular based therapy approaches.
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PMID:Drosophila melanogaster as a model organism of brain diseases. 1933 15

The mammalian target of rapamycin (mTOR) and its associated cell signaling pathways have garnered significant attention for their roles in cell biology and oncology. Interestingly, the explosion of information in this field has linked mTOR to neurological diseases with promising initial studies. mTOR, a 289 kDa serine/threonine protein kinase, plays an important role in cell growth and proliferation and is activated through phosphorylation in response to growth factors, mitogens, and hormones. Growth factors, amino acids, cellular nutrients, and oxygen deficiency can down-regulate mTOR activity. The function of mTOR signaling is mediated primarily through two mTOR complexes: mTORC1 and mTORC2. mTORC1 initiates cap-dependent protein translation, a rate-limiting step of protein synthesis, through the phosphorylation of the targets eukaryotic initiation factor 4E-binding protein 1 (4EBP1) and p70 ribosomal S6 kinase (p70S6K). In contrast, mTORC2 regulates development of the cytoskeleton and also controls cell survival. Although closely tied to tumorigenesis, mTOR and the downstream signaling pathways are significantly involved in the central nervous system (CNS) with synaptic plasticity, memory retention, neuroendocrine regulation associated with food intake and puberty, and modulation of neuronal repair following injury. The signaling pathways of mTOR also are believed to be a significant component in a number of neurological diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, tuberous sclerosis, neurofibromatosis, fragile X syndrome, epilepsy, traumatic brain injury, and ischemic stroke. Here we describe the role of mTOR in the CNS and illustrate the potential for new strategies directed against neurological disorders.
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PMID:Mammalian target of rapamycin: hitting the bull's-eye for neurological disorders. 2130 46

This patent application claims that inhibition of p21-activated kinases (PAK) reverses, partially reverses or delays clinical signs in neurological conditions (main claim for Huntington's disease (HD), substance abuse and addiction, Parkinson's disease, depression, bipolar disorder, anxiety disorder, posttraumatic stress disorder and neurofibromatosis). Several compounds with a pyrido-[2,3-d]pyrimidine-7(8H)-one core and high affinity to the catalytic domain of PAK1-4 are described in the patent. These PAK inhibitors are hypothesized to exert beneficial effects on clinical symptoms via modulation of dendritic spine morphology and/or synaptic function. Preliminary preclinical data suggest that PAK inhibition may be an interesting approach for the treatment of HD, neurofibromatosis and fragile X syndrome, while data for other neurological conditions are missing. Current limitations call for a comprehensive characterization of the role of PAK dysfunction in neurological disorders before further testing the effect of PAK inhibitors in relevant preclinical models. If ever, it will probably take many years before the most promising compounds will head to the clinic for further assessment in patients with neurological disorders.
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PMID:Methods for treating neurological conditions (WO2011159945). 2269 32

Mammalian/mechanistic target of rapamycin (mTOR) is a serine-threonine kinase that controls several important aspects of mammalian cell function. mTOR activity is modulated by various intra- and extracellular factors; in turn, mTOR changes rates of translation, transcription, protein degradation, cell signaling, metabolism, and cytoskeleton dynamics. mTOR has been repeatedly shown to participate in neuronal development and the proper functioning of mature neurons. Changes in mTOR activity are often observed in nervous system diseases, including genetic diseases (e.g., tuberous sclerosis complex, Pten-related syndromes, neurofibromatosis, and Fragile X syndrome), epilepsy, brain tumors, and neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, and Huntington's disease). Neuroscientists only recently began deciphering the molecular processes that are downstream of mTOR that participate in proper function of the nervous system. As a result, we are gaining knowledge about the ways in which aberrant changes in mTOR activity lead to various nervous system diseases. In this review, we provide a comprehensive view of mTOR in the nervous system, with a special focus on the neuronal functions of mTOR (e.g., control of translation, transcription, and autophagy) that likely underlie the contribution of mTOR to nervous system diseases.
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PMID:Molecular neurobiology of mTOR. 2788 78

Monacolin K (MK) is the principal active substance in Monascus-fermentation products (e.g. red yeast rice). MK is effective in reducing cholesterol levels in humans and has been widely used as a lipid-lowering drug. The mechanism for this is through a high degree of competitive inhibition of the rate-limiting enzyme HMG-CoA reductase (HMGR) in the cholesterol synthesis pathway. In addition to lowering blood lipid levels, MK also prevents colon cancer, acute myeloid leukemia and neurological disorders such as Parkinson's disease and type I neurofibromatosis. The aim of this manuscript is to comprehensively review the progress in the study of the biological activity of MK and its imechanism of action in reducing blood lipid concentration, prevention of cancer and its neuroprotective, anti-inflammatory and antibacterial properties. This review provides a reference for future applications of MK in functional foods and medicine.
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PMID:An overview of the bioactivity of monacolin K / lovastatin. 3120 6