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)

We have recently shown that there is a previously unsuspected link between the intracellular inclusions seen in several major chronic human degenerative diseases, including neurodegenerative diseases: the inclusions showing ubiquitin immunoreactivity. The conditions include Parkinson's disease, motor neurone disease, Alzheimer's disease, Pick's disease, and alcoholic liver disease as well as cerebellar astrocytomas and a myopathy. The inclusions found in these diseases are reported to contain intermediate filaments: neurofilaments are associated with Lewy bodies in Parkinson's disease, Pick's bodies in Pick's disease and neurofibrillary tangles in Alzheimer's disease, cytokeratins are found in Mallory bodies in alcoholic liver disease, glial fibrillary acidic proteins and vimentin are found in Rosenthal fibres in astrocytomas, and desmin is found in cytoplasmic bodies in cytoplasmic body myopathy. Therefore five classes of intermediate filaments are found in inclusions which also contain ubiquitin immunoreactivity; we have also shown that ubiquitin immunoreactivity is present in vesicles in some areas of granulovacuolar degeneration in Alzheimer's disease. Protein ubiquitination is considered a signal for extralysosomal protein degradation, (although ubiquitination may have several other important functions). We have recently shown that intermediate filaments are involved in protein sequestration before degradation by lysosomally mediated autophagy: therefore intermediate filament-containing ubiquitinated inclusions may be the hallmarks of cellular attempts to eliminate pathogenic insults by the activation of both extralysosomal and lysosomal mechanisms of intracellular protein degradation. We have recently been able to reproduce, at least in part, some of the clinical observations in tissue culture cells. Ubiquitinated protein conjugates accumulate in lysosomes in fibroblasts treated with the lysosomal cysteine protease inhibitor E-64, which may mimic aspects of granulovacuolar degeneration.
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PMID:Intermediate filaments and ubiquitin: a new thread in the understanding of chronic neurodegenerative diseases. 255 42

The molecular pathology of chronic degenerative disease is not understood. Generally there must be two related, but opposing, processes: the direct deleterious effects of the pathogenic insult which can be chemical or viral and a cellular cytoprotective response to the insult. We have recently shown that there is a previously unsuspected link between the intracellular inclusions seen in some major chronic degenerative diseases: the inclusions contain ubiquitin immunoreactivity. The conditions include Parkinson's disease, motor neurone disease, Alzheimer's disease and alcoholic liver disease as well as astrocytomas and a myopathy. Protein ubiquitination is considered a signal for extra-lysosomal protein degradation although ubiquitin-protein conjugation may have several other important functions. Intermediate filaments are a component of some of the inclusions in diseased cells; we have previously reported that they are involved in protein sequestration for degradation by lysosomally mediated autophagy. Therefore, intermediate-filament-containing ubiquitinated inclusions may be hallmarks of cellular attempts to eliminate pathogenic insults by activating protein degradation mechanisms. Ubiquitinated inclusions could also be a hallmark of viral infections: they are in polio-virus-infected anterior horn neurones and Epstein-Barr-transformed lymphoblastoid cells. Some of the clinical observations can be reproduced experimentally in tissue culture cells. The implications of the combined clinical and experimental observations for cell sanitization and protein catabolism will be discussed.
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PMID:Intermediate filament-ubiquitin diseases: implications for cell sanitization. 255 34

Polyclonal antibodies were raised which have a high affinity for conjugated ubiquitin. Immunocytochemistry was performed on paraffin sections of tissues showing well-characterized inclusion bodies. Ubiquitin was found as a component of the intermediate filament inclusion bodies characteristic of several major diseases including Lewy bodies of Parkinson's disease, Pick bodies of Pick's disease, Mallory bodies of alcoholic liver disease, cytoplasmic bodies of a specific myopathy, and Rosenthal fibres within astrocytes. Ubiquitin was also present in the three histological lesions characteristic of Alzheimer's disease. These observations suggest a fundamental role for ubiquitin in the formation of intermediate filament inclusion bodies in man, and have implications regarding the pathogenesis of these important diseases.
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PMID:Ubiquitin is a common factor in intermediate filament inclusion bodies of diverse type in man, including those of Parkinson's disease, Pick's disease, and Alzheimer's disease, as well as Rosenthal fibres in cerebellar astrocytomas, cytoplasmic bodies in muscle, and mallory bodies in alcoholic liver disease. 283 58

In the last years, considerable advances have been made in the study of the proteins and polypeptides of the cytoskeleton, and its three main components: microfilaments (MF), intermediate filaments (IMF) and microtubules (MT). The principal properties of these elements and those of many associated proteins are recalled. The actin MF are mainly involved in cell contractility, the IMF in cell shape, while the MT and their associated proteins are involved in intracellular transport. Some pathological modifications of the cytoskeleton will be considered. In the liver, accumulations of keratin result in the formation of Mallory's hyalin, found in several types of cirrhosis and hepatomas. In muscle, accumulations of desmin are observed in various myopathies. An accumulation of alpha-actinin at the Z bands characterizes nemalin myopathy. In several forms of hemolytic anemias, alterations of the membranous cytoskeletal components of the red blood cells--spectrin, ankyrin, actin--may explain their abnormal shape and excessive fragility. In the nervous system, many pathological conditions are related to abnormal cytoskeletal components. In Parkinson's disease, Lewy bodies are an accumulation of neurofilaments (IMF). In Alzheimer's disease, and some related conditions, the intraneuronal tangles are associated with modifications of MT and neurofilaments. The role of MT and in particular of the MT-associated protein tau, as demonstrated recently, confirms the involvement of the MT. The observed disturbances of MT-related axonal flow may explain some of the known functional changes in these forms of dementia.
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PMID:[Pathology of the cytoskeleton]. 329 78

Spinocerebellar degeneration is a heredofamilial disease of unknown aetiology. The shape of erythrocytes as revealed by scanning electron microscopy was studied in this disease. Echinocytes I, as defined by Bessis, were seen more frequently in spinocerebellar degeneration than in age and sex matched controls (7.2 +/- 1.5% in spinocerebellar degeneration, 3.4 +/- 1.2% in controls, p less than 0.001), Parkinson's disease, motor neuron disease, myopathy, and Huntington's chorea. Erythrocyte deformability was impaired to a greater extent in spinocerebellar degeneration than in the controls when the pH was raised from 7.2 to 8.0; Echinocytes I in spinocerebellar degeneration increased from 8.4 +/- 0.6 to 15.4 +/- 2.4%, in the control group from 2.8 +/- 1.2 to 13.3 +/- 2.1%. In spinocerebellar degeneration no significant correlation was found between the level of serum low density lipoprotein and the number of Echinocytes I. In both groups there was a significant correlation between the occurrence of Echinocytes I and age, and the difference of Echinocytes I was greater in aged subjects in spinocerebellar degeneration. The data suggest that membrane abnormality in erythrocytes exists in spinocerebellar degeneration and may be accelerated with the advance of age.
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PMID:Scanning electron microscopy studies of erythrocytes in spinocerebellar degeneration. 670 72

In the last 4 years much progress has been made in the understanding of mitochondrial disorders. Point-mutations, deletions and depletion of the mitochondrial genome are associated with disorders like Leber's disease, MERRF (Myoclonus Epilepsia with Ragged Red Fibers), MELAS (mitochondrial Myopathy, Encephalopathy, Lactic acidosis and Stroke-like episodes) and several others. Recently, mitochondrial dysfunctions have been also related to neurodegenerative disorders like Parkinson's disease and to aging. Since the brain depends mostly on mitochondrial energy supply, mitochondrial dysfunctions may affect the nervous system more severely than other tissues causing or worsening diseases and playing a role in the biological deterioration of aging. Furthermore, the mitochondrial energy supply is associated with the production of highly reactive oxygen species. Ninety-five percent of the molecular oxygen is metabolized within the mitochondria by the electron-transport chain so that mitochondria are highly exposed to oxidative stress which may damage selected neuronal populations. Oxygen radicals created during respiration induce mitochondrial dysfunction which accelerates the production of more deleterious species of oxygen. The latter step further increases mitochondrial malfunction, thus intensifying and perpetuating the cycle. These two mechanisms combined may lead to cell death in brain and other tissues with high metabolic rate. Therefore, in neurodegenerative disorders such as Parkinson's disease mitochondrial dysfunction and oxidative stress may cause or worsen the clinical features.
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PMID:Oxidative stress and mitochondrial dysfunction in neurodegeneration. 784 18

Neurogenic dysphagia results from sensorimotor impairment of the oral and pharyngeal phases of swallowing due to a neurologic disorder. The symptoms of neurogenic dysphagia include drooling, difficulty initiating swallowing, nasal regurgitation, difficulty managing secretions, choke/cough episodes while feeding, and food sticking in the throat. If unrecognized and untreated, neurogenic dysphagia can lead to dehydration, malnutrition, and respiratory complications. The symptoms of neurogenic dysphagia may be relatively inapparent on account of both compensation for swallowing impairment and diminution of the laryngeal cough reflex due to a variety of factors. Patients with symptoms of oropharyngeal dysphagia should undergo videofluoroscopy of swallowing, which in the case of neurogenic dysphagia typically reveals impairment of oropharyngeal motor performance and/or laryngeal protection. The many causes of neurogenic dysphagia include stroke, head trauma, Parkinson's disease, motor neuron disease and myopathy. Evaluation of the cause of unexplained neurogenic dysphagia should include consultation by a neurologist, magnetic resonance imaging of the brain, blood tests (routine studies plus muscle enzymes, thyroid screening, vitamin B12 and anti-acetylcholine receptor antibodies), electromyography/nerve conduction studies, and, in certain cases, muscle biopsy or cerebrospinal fluid examination. Treatment of neurogenic dysphagia involves treatment of the underlying neurologic disorder (if possible), swallowing therapy (if oral feeding is reasonably safe to attempt) and gastrostomy (if oral feeding is unsafe or inadequate).
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PMID:Dysphagia associated with neurological disorders. 820 77

To clarify the mechanism of brain impairment in Machado-Joseph disease (MJD), we measured the cerebrospinal fluid (CSF) levels of substance P in 7 patients (mean age 45.7 +/- 12.09 years) with this disease. Four patients had type I and three had type II disease. Findings were compared with those obtained in 14 age-matched controls, 8 patients with Parkinson's disease, 7 patients with multiple system atrophy, and 6 patients with myopathy. The CSF level of substance P was significantly (p = 0.0000) lower in the patients with MJD, being 44.5% of the control value. However, the mean CSF levels of substance P in the patients with Parkinson's disease, multiple system atrophy, or myopathy did not differ significantly from that in the control subjects. The alteration in the CSF level of substance P may be related to the neurological impairment observed in MJD.
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PMID:Decreased cerebrospinal fluid levels of substance P in Machado-Joseph disease. 890 28

Virtually all cells in humans depend on mitochondrial oxidative phosphorylation to generate energy, accounting for the remarkable diversity of clinical disorders associated with mitochondrial DNA mutations. However, certain tissues are particularly susceptible to mitochondrial dysfunction, resulting in recognizable clinical syndromes. Mitochondrial DNA mutations have been linked to seizures, strokes, optic atrophy, neuropathy, myopathy, cardiomyopathy, sensorineural hearing loss, diabetes mellitus, and other clinical features. Mitochondrial DNA mutations also may play an important role in aging, as well as in common age-related neurodegenerative disorders such as Parkinson's disease. Therefore, it is becoming increasingly important for clinicians to recognize the clinical syndromes suggestive of a mitochondrial disorder, and to understand the unique features of mitochondrial genetics that complicate diagnosis and genetic counseling.
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PMID:Mitochondrial disorders: clinical and genetic features. 1007 67

Though mitochondria have been a major source of energy production in eukaryotae since 15-20 billion years previously, existence of disorders due to primary abnormalities of their DNA has not been known until very recent years. In 1962, Luft et al reported the first case of such myopathy, and another case reported in 1967 by Shy et al was also the first case of generalized disorder with mitochondrial abnormalities. Since then, many case reports have followed including MELAS and other encephalomyopathies. Finally, in 1989, deletion of mitochondria DNA was found by Folt et al. Today, these disorders were able to be classified as follows: 1) LHON and A1555G type deafness as strictly limited non-syndromic type, 2) encephalomyopathies and their incomplete forms due to common and other deletions of mitochondria DNA, 3) encephalomyopathies and their incomplete forms including MIDD, diabetes mellituis, cardiomyopathy, deafness due to point mutations of mitochondria DNA related MELAS and others, 4) Neurodegenerative types including Parkinson's disease, Alzheimer's disease, cerebellar degeneration, and amyotrophic lateral sclerosis, or neurologic disorders mimic to such diseases, 5) Mitochondrial involvement not due to primary abnormalities of mitochondria DNA. Possible mechanisms were discussed, but sufficient knowledge is lacking so far to clarify pathophysiology of these disorders and the role of deleterious DNA in aging. Possible effective therapeutic strategies were also discussed, but further development of research works on these disorders in the 21st century are needed to answer these questions.
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PMID:[Current and future aspects of mitochondrial diseases]. 1079 Oct 75


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