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)

The etiology of a high-incidence focus of amyotrophic lateral sclerosis and parkinsonism-dementia (ALS/P-D) in south West Papua (Irian Jaya, Indonesia), first described in the 1960s and 1970s, has been attributed to mineral deficiencies, hyperparathyroidism, and metal neurotoxicity arising from reliance on drinking water obtained from springs and shallow wells. More recent visits (1987 and 1990) to the south West Papua focus of neurodegenerative disease cast doubt on this explanation by revealing changes in disease prevalence in communities with an unchanged water supply. These communities have experienced a dramatic decline in ALS and a reversal in the relative prevalence of ALS and parkinsonism. The extrapyramidal disorder can be distinguished from Parkinson disease by pyramidal features (and dementia) reminiscent of Guam P-D. Topical use of cycad seed (termed kurru) gametophyte to treat large skin lesions is advanced as a plausible but unproven etiologic factor. Medicinal use of untreated cycad seed (Cycas sp.) has also been linked with ALS foci in Japan (oral use) and Guam (topical use), with the additional consumption on Guam of food items prepared from Cycas sp. seed or animals that consume cycad seed components.
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PMID:On the decline and etiology of high-incidence motor system disease in West Papua (southwest New Guinea). 1609 1

Movement disorders are common neurological illnesses among the elderly. These include essential tremor, Perkinsonian disorders and chorea of different aetiologies. Parkinsonian disorders can be divided into two major groups of disorders--classical idiopathic Parkinson's disease and Parkinson plus syndrome. The most common and important cause of Parkinsonism is idiopathic Parkinson's disease. Idiopathic Parkinson's disease is most confidently clinically diagnosed if we follow the United Kingdom Parkinson's Disease Society Brain Bank Diagnostic Criteria for Parkinson's disease. The most common degnerative diseases, which minic idiopathic Parkinson's disease are collectively called Parkinson plus syndrome. The most important diseases comprising Parkinson plus syndrome are: progressive supranuclear palsy, multiple system atrophy, cortical-basal ganglionic degneration, diffuse Lewy body disease and Parkinson-dementia-ALS complex. In India the prevalence of Parkinson's disease varied markedly from one study to another. The prevalence rate is high among the urban Parsi community of Mumbai. Incidence and prevalence of Parkinson's disease increase with increasing age. Some risk factors for Parkinson's disease have been narrated briefly. As the number of cases of Parkinsonism is likely to increase along with increasing population, the general practitioners or consultant physicans should have to play a greater role referring the cases to attend neurologists or movement disorder clinic early.
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PMID:Is Parkinson's disease a homogeneous disorder--what is the burden of Parkinson's disease in India. 1617 91

Here is proposed a hypothesis that a completely unsuspected biology exists for pathogenic spirochetes, namely that the cystic spirochetal forms (long thought to be static and resting or just a dormant cohort) actually are capable of killing mammalian host cells. At least two "lethal" scenarios are proposed; first, the host cell destruction from the "inside out" by small caliber cystic forms invading the host cell cytoplasm, and second host cell destruction by engulfment of entire host cells by large caliber cystic spirochetal forms. Conventional thinking about spirochetal cyst forms is divided between two polar spheres of influence; one a majority community that completely denies the existence of spirochetal cyst forms, and a second group of academically persecuted individuals who accepts the precepts of such antebellum scientists as Schaudinn, Hoffman, Dutton, Levaditi, Balfour, Fantham, Noguchi, McDonough, Hindle, Steiner, Ingraham, Coutts, Hampp, Warthin, Ovcinnikov, and Delamater. Microscopic images of cystic spirochetes are difficult to ignore, but as has been the case in this century, academic "endowments" have nearly expunged all cystic spirochetal image data from the current textbook versions of what is the truth about the spirochetaceae. If the image database from the last century is obliterated; many opportunities to diagnose will be lost. Variously sized cystic spirochetal profiles within diseased nerve cells explain the following structures: Lewy body of Parkinson's disease, Pick body, ALS spherical body, Alzheimer plaque. Borrelia infection is therefore a unifying concept to explain diverse neurodegenerative diseases, based not entirely on a corkscrew shaped profile in diseased tissue, but based on small, medium and large caliber rounded cystic profiles derived from pathogenic spirochetes which are..."hiding in plain sight".
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PMID:Spirochetal cyst forms in neurodegenerative disorders,...hiding in plain sight. 1682 36

Neuronal DNA repair remains one of the most exciting areas for investigation, particularly as a means to compare the DNA repair response in mitotic (cancer) vs. post-mitotic (neuronal) cells. In addition, the role of DNA repair in neuronal cell survival and response to aging and environmental insults is of particular interest. DNA damage caused by reactive oxygen species (ROS) such as generated by mitochondrial respiration includes altered bases, abasic sites, and single- and double-strand breaks which can be prevented by the DNA base excision repair (BER) pathway. Oxidative stress accumulates in the DNA of the human brain over time especially in the mitochondrial DNA (mtDNA) and is proposed to play a critical role in aging and in the pathogenesis of several neurological disorders including Parkinson's disease, ALS, and Alzheimer's diseases. Because DNA damage accumulates in the mtDNA more than nuclear DNA, there is increased interest in DNA repair pathways and the consequence of DNA damage in the mitochondria of neurons. The type of damage that is most likely to occur in neuronal cells is oxidative DNA damage which is primarily removed by the BER pathway. Following the notion that the bulk of neuronal DNA damage is acquired by oxidative DNA damage and ROS, the BER pathway is a likely area of focus for neuronal studies of DNA repair. BER variations in brain aging and pathology in various brain regions and tissues are presented. Therefore, the BER pathway is discussed in greater detail in this review than other repair pathways. Other repair pathways including direct reversal, nucleotide excision repair (NER), mismatch repair (MMR), homologous recombination and non-homologous end joining are also discussed. Finally, there is a growing interest in the role that DNA repair pathways play in the clinical arena as they relate to the neurotoxicity and neuropathy associated with cancer treatments. Among the numerous side effects of cancer treatments, major clinical effects include neurocognitive dysfunction and peripheral neuropathy. These symptoms occur frequently and have not been effectively studied at the cellular or molecular level. Studies of DNA repair may help our understanding of how those cells that are not dividing could succumb to neurotoxicity with the clinical manifestations discussed in the following article.
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PMID:DNA repair in neurons: so if they don't divide what's to repair? 1687 37

Multiple sclerosis is considered a disease of myelin destruction; Parkinson's disease (PD), one of dopaminergic neuron depletion; ALS, a disease of motor neuron death; and Alzheimer's, a disease of plaques and tangles. Although these disorders differ in important ways, they also have common pathogenic features, including inflammation, genetic mutations, inappropriate protein aggregates (e.g., Lewy bodies, amyloid plaques), and biochemical defects leading to apoptosis, such as oxidative stress and mitochondrial dysfunction. In most disorders, it remains uncertain whether inflammation and protein aggregation are neurotoxic or neuroprotective. Elucidating the mechanisms that orchestrate neuronal diseases should facilitate development of neuroprotective and neurorestorative strategies.
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PMID:Neurodegeneration and neuroprotection in multiple sclerosis and other neurodegenerative diseases. 1698 47

Nitric oxide (NO) is a short lived diatomic free radical species synthesized by nitric oxide synthases (NOS). The physiological roles of NO depend on its local concentrations as well as availability and the nature of downstream target molecules. At low nanomolar concentrations, activation of soluble guanylyl cyclase (sGC) is the major event initiated by NO. The resulting elevation in the intracellular cyclic GMP (cGMP) levels serves as signals for regulating diverse cellular and physiological processes. The participation of NO and cGMP in diverse physiological processes is made possible through cell type specific spatio-temporal regulation of NO and cGMP synthesis and signal diversity downstream of cGMP achieved through specific target selection. Thus cyclic GMP directly regulates the activities of its downstream effectors such as Protein Kinase G (PKG), Cyclic Nucleotide Gated channels (CNG) and Cyclic nucleotide phosphodiesterases, which in turn regulate the activities of a number of proteins that are involved in regulating diverse cellular and physiological processes. Localization and activity of the NO-cGMP signaling pathway components are regulated by G-protein coupled receptors, receptor and non receptor tyrosine kinases, phosphatases and other signaling molecules. NO also serves as a powerful paracrine factor. At micromolar concentrations, NO reacts with superoxide anion to form reactive peroxinitrite, thereby leading to the oxidation of important cellular proteins. Extensive research efforts over the past two decades have shown that NO is an important modulator of axon outgrowth and guidance, synaptic plasticity, neural precursor proliferation as well as neuronal survival. Excessive NO production as that evoked by inflammatory signals has been identified as one of the major causative reasons for the pathogenesis of a number of neurodegenerative diseases such as ALS, Alzheimers and Parkinson diseases. Regenerative therapies involving transplantation of embryonic stem cells (ES cells) and ES cell derived lineage committed neural precursor cells have recently shown promising results in animal models of Parkinson disease (PD). Recent studies from our laboratory have shown that a functional NO-cGMP signaling system is operative early during the differentiation of embryonic stem cells. The cell type specific, spatio-temporally regulated NO-cGMP signaling pathways are well suited for inductive signals to use them for important cell fate decision making and lineage commitment processes. We believe that manipulating the NO-cGMP signaling system will be an important tool for large scale generation of lineage committed precursor cells to be used for regenerative therapies.
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PMID:NO-cGMP signaling and regenerative medicine involving stem cells. 1704 68

Neural stem cells (NSCs)of the central nervous system (CNS) have recently received a great deal of attention and interest for their therapeutic potential for neurological disorders. NSCs are defined as CNS progenitor cells that have the capacity for self-renewal and multipotent potential to become neurons or glial cells. Recent studies have shown that NSCs isolated from mammalian CNS including human can be propagated in vitro and then implanted into the brain of animal models of human neurological disorders. Recently, we have generated clonally derived immortalized human NSC cell lines via a retroviral vector encoded with v-myc oncogene. One of the human NSC lines, HB1.F3, was utilized in stem-cell based therapy in animal models of human neurological disorders. When F3 human NSCs were implanted into the brain of murine models of lysosomal storage diseases, stroke, Parkinson disease, Huntington disease or stroke, implanted F3 NSCs were found to migrate to the lesion sites, differentiate into neurons and glial cells, and restore functional deficits found in these neurological disorders. In animal models of brain tumors, F3 NSCs could deliver a bioactive therapeutically relevant molecules to effect a significant anti-tumor response intracranial tumor mass. Since these genetically engineered human NSCs are immortalized and continuously multiplying, there would be limitless supply of human neurons for treatment for patients suffering from neurological disorders including stroke, Parkinson disease, Huntington disease, ALS, multiple sclerosis and spinal cord injury. The promising field of stem cell research as it applies to regenerative medicine is still in infancy, but its potential appears limitless, and we are blessed to be involved in this exciting realm of research.
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PMID:Genetically engineered human neural stem cells for brain repair in neurological diseases. 1730 60

We investigated retrospectively 157 neurological patients who underwent percutaneous endoscopic gastrostomy (PEG) since 2003 May to 2006 January, focusing on their neurological diagnosis, complication, relation to ventilatory support and survival prognosis. Among 157 patients, 42 patients had amyotrophic lateral sclerosis, 39 Parkinson's disease, and 27 multiple system atrophy. The percentage for the neurodegenerative diseases was 68.0%. The most frequent complication during PEG procedure was transient hypoxia (8 patients), three of whom needed oxygen therapy, but no patients received emergent artificial ventilation. After PEG. six patients experienced accidental self-removal of the catheter, but there was no subsequent peritonitis. Seven patients were on tracheostomy positive-pressure ventilation during PEG. and two on non-invasive intermittent positive-pressure ventilation around the PEG period, in all of whom the PEG was carried out without any trouble. Investigation on survival after PEG showed that nine ALS patients died within six months because of respiratory failure. We conclude that PEG for neurological patients was generally performed safely. For ALS patients, however, respiratory function should be carefully monitored, and PEG should be performed in ALS patients before their respiratory function becomes worse.
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PMID:[Percutaneous endoscopic gastrostomy in patients with intractable neurological diseases--retrospective study of the indication, complication and prognosis]. 1801 13

In the mountains of Peru, globular colonies of Nostoc commune (Nostocales) are collected in the highland lakes by the indigenous people, who call them llullucha. They are consumed locally, traded for maize, or sold, eventually entering the folk markets of Cusco and other neighboring cities. Throughout highland Peru, Nostoc commune is highly salient as a seasonal dietary item, being eaten alone, or in picante -- a local stew -- and is said to be highly nutritious. Nostoc commune has been known to produce unusual amino acids, including those of the mycosporine group, which possibly function to prevent UV damage. We analyzed 21 different Nostoc commune spherical colonies from 7 different market collections in the Cusco area for the presence of beta-N-methylamino-L-alanine (BMAA), a neurotoxic amino acid produced by diverse taxa of cyanobacteria, using four different analytical techniques (HPLC-FD, UPLC-UV, UPLC/MS, LC/MS/MS). We found using all four techniques that BMAA was present in the samples purchased in the Peruvian markets. Since BMAA has been putatively linked to neurodegenerative illness, it would be of interest to know if the occurrence of ALS, Alzheimer's, or Parkinson's Disease is greater among individuals who consume llullucha in Peru.
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PMID:Cyanobacteria (Nostoc commune) used as a dietary item in the Peruvian highlands produce the neurotoxic amino acid BMAA. 1849 96

Cell death plays an important role both in shaping the developing nervous system and in neurological disease and traumatic injury. In spite of their name, death receptors can trigger either cell death or survival and growth. Recent studies implicate five death receptors--Fas/CD95, TNFR1 (tumor necrosis factor receptor-1), p75NTR (p75 neurotrophin receptor), DR4, and DR5 (death receptors-4 and -5)--in different aspects of neural development or degeneration. Their roles may be neuroprotective in models of Parkinson's disease, or pro-apoptotic in ALS and stroke. Such different outcomes probably reflect the diversity of transcriptional and posttranslational signaling pathways downstream of death receptors in neurons and glia.
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PMID:Signaling by death receptors in the nervous system. 1872 96


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