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)

Germ-line and somatic mtDNA mutations are hypothesized to act together to shape our history and our health. Germ-line mtDNA mutations, both ancient and recent, have been associated with a variety of degenerative diseases. Mildly to moderately deleterious germ-line mutations, like neutral polymorphisms, have become established in the distant past through genetic drift but now may predispose certain individuals to late-onset degenerative diseases. As an example, a homoplasmic, Caucasian, tRNA(Gln) mutation at nucleotide pair (np) 4336 has been observed in 5% of Alzheimer disease and Parkinson disease patients and may contribute to the multifactorial etiology of these diseases. Moderately to severely deleterious germ-line mutations, on the other hand, appear repeatedly but are eliminated by selection. Hence, all extant mutations of this class are recent and associated with more devastating diseases of young adults and children. Representative of these mutations is a heteroplasmic mutation in MTND6 at np 14459 whose clinical presentations range from adult-onset blindness to pediatric dystonia and basal ganglial degeneration. To the inherited mutations are added somatic mtDNA mutations which accumulate in random arrays within stable tissues. These mutations provide a molecular clock that measures our age and may cause a progressive decline in tissue energy output that could precipitate the onset of degenerative diseases in individuals harboring inherited deleterious mutations.
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PMID:Mitochondrial DNA sequence variation in human evolution and disease. 809 Jul 16

Swollen, bulbous-shaped (dystrophic) neurites are a common pathologic feature of Alzheimer's disease (AD) and represent one of the most abundant neuritic abnormalities within the brains of patients with this disease. In the present study, we sought to determine whether the dystrophic neurites which are observed in association with senile plaques are unique to AD or whether they are characteristic of a more generalized process of neuritic and/or neuronal degeneration which can be observed in other neurodegenerative diseases. To accomplish this, we examined post-mortem brain material from patients with AD, Parkinson's disease (PD), Parkinson's disease with associated AD, Parkinson's disease with dementia yet without AD pathology, Huntington's disease (HD), Pick's disease and normal age-matched controls (NC). Using a battery of antibodies to amyloid beta-protein (A beta P), paired-helical filaments (PHF), tyrosine hydroxylase, substance P, neurotensin, and somatostatin we found that immunolabeled dystrophic neurites of the type characteristically observed in AD, were seen only in cases and in brain regions where A beta P deposition was present. More specifically, brain areas known to display severe afferent and/or local degenerative changes such as the caudate and putamen in all three PD groups, the caudate in the HD cases, and the temporal cortex in the HD and Pick's cases were conspicuously free of these swollen neurites unless A beta P deposition was also present.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alzheimer's disease-like dystrophic neurites characteristically associated with senile plaques are not found within other neurodegenerative diseases unless amyloid beta-protein deposition is present. 809 26

Reaction time in normal subjects is known to increase in a log-linear fashion relative to the number of alternative choices. However, this relationship (formalized as "Hick's law") has received limited investigation in populations with neurological cognitive impairment. The present study used timed sorting of standard playing cards to test Hick's law for 20 young control subjects, and 20 each of age-matched elderly subjects with Alzheimer disease, Parkinson disease, and no cognitive abnormalities. Although Parkinson patients were slowest in the simple tasks of dealing out the cards and sorting by color, Alzheimer patients showed the greatest slowing for the more cognitively complex conditions of sorting by suit and rank of the cards. The performance of all four groups followed Hick's law in displaying a significant linear relationship between response time and log2 of the number of choices. These findings suggest that, although limitations of information-processing speed in Alzheimer and Parkinson disease affected choice response time, there may be sparing of fundamental cognitive organization in these disorders.
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PMID:Application of Hick's law of response speed in Alzheimer and Parkinson diseases. 836 25

This paper reviews the changes in dopaminergic, cholinergic and glutamatergic neurotransmission, which occur in the aging of the central nervous system (CNS) and in age-related diseases: Parkinson's disease (PD) and Alzheimer's disease (AD). Dopaminergic neurotransmission is impaired with age due to degeneration of the substantia nigra pars compacta neurons and reduction of the density of postsynaptic D1 and D2 dopamine receptors in the striatum. PD is believed to be caused by a severe loss of dopaminergic neurons, which leads to nearly complete depletion of dopamine in the striatum, particularly in the putamen. The supersensitivity of postsynaptic dopamine receptors, reported by some authors, may result from compensatory mechanisms to degeneration of dopaminergic neurons. The role of aging in PD is also discussed in the paper. An interest in the role of the cholinergic and glutamatergic systems in aging results from the concept that the development of AD is due to the pathology of these systems. The data on cholinergic neurotransmission are controversial and imply that aging affects rather slightly both neurons and cholinergic receptors. In AD, however, severe degeneration of cholinergic neurons of the basal nucleus of Meynert, leading to the impairment of cholinergic neurotransmission in the hippocampus and the cerebral cortex, has been observed. In AD degeneration of glutamatergic neurons and subsensitivity of some excitatory amino acids receptors in the hippocampus and the cerebral cortex may lead to dementia. However, an increase in the glutamate release from presynaptic glutamatergic terminals may be responsible for neuronal degeneration in AD. The role of the beta-amyloid protein in a neurodegenerative activity of glutamic acid is discussed.
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PMID:Disturbances in neurotransmission processes in aging and age-related diseases. 840 65

The Chamorro population of the island of Guam is highly susceptible to a disease called lytico-bodig (LB), which clinically resembles a mixture of amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer disease (AD). The disease is characterized by the widespread development of neurofibrillary tangles in the central nervous system. These tangles have an immunohistochemical profile indistinguishable from that seen in AD. We studied by immunohistochemistry the occurrence of intracellular and extracellular neurofibrillary tangles in LB in the entorhinal cortex, hippocampus and substantia nigra using antibodies to tau protein and ubiquitin. We also studied the relationship of these tangles to amyloid precursor protein (APP) and its beta-amyloid fragment (BAP), using multiple antibodies to BAP and other APP sequences. In advanced cases of LB, the development of neurofibrillary tangles was far more severe than in advanced cases of AD. Virtually all neurons of CA-1 and the subiculum were lost and only ghost tangles remained. In areas dominated by such extracellular tangles, BAP deposits were frequently observed developing around the fibers of ghost tangles. In some cases, the deposits covered only a few of the fibers, but in others, they seemed to envelope the complete tangle. The deposits were thioflavin S and Congo red positive, indicating that the BAP was in a consolidated form. We describe these entities as "tangle-associated amyloid deposits". Such BAP deposits have previously been described in some cases of AD, dementia pugilistica and LB. However, we found them in all cases of LB with dementia in the hippocampal-entorhinal areas and in most cases in the substantia nigra. They do not evolve from diffuse BAP deposits since they are remote from them, and they do not trap dystrophic neurites. The fact that extracellular tangle material can act as a nidus for BAP build-up in LB suggests that further consideration needs to be given to the ways in which extracellular BAP deposits are formed.
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PMID:Relationship of amyloid beta/A4 protein to the neurofibrillary tangles in Guamanian parkinsonism-dementia. 852 3

Defects in mitochondrial energy production have been implicated in several neurodegenerative disorders, such as Parkinson disease and amyotrophic lateral sclerosis. To study the contribution of mitochondrial defects to Alzheimer disease and schizophrenia, cytochrome-c oxidase (COX) activity and levels of the mtDNA4977 deletion in postmortem brain tissue specimens of patients were compared with those of asymptomatic age-matched controls. No difference in COX activity was observed between Alzheimer patients and controls in any of five brain regions investigated. In contrast, schizophrenic patients had a 63% reduction of the COX activity in the nucleus caudatus (P < 0.0001) and a 43% reduction in the cortex gyrus frontalis (P < 0.05) as compared to controls. The average levels of the mtDNA4977 deletion did not differ significantly between Alzheimer patients and controls, and the deletion followed similar modes of accumulation with age in the two groups. In contrast, no age-related accumulation of mtDNA deletions was found in schizophrenic patients. The reduction in COX activity in schizophrenic patients did not correlate with changes in the total amount of mtDNA or levels of the mtDNA4977 deletion. The lack of age-related accumulation of the mtDNA4977 deletion and reduction in COX activity suggest that a mitochondrial dysfunction may be involved in the pathogenesis of schizophrenia.
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PMID:Decreased cytochrome-c oxidase activity and lack of age-related accumulation of mitochondrial DNA deletions in the brains of schizophrenics. 853 74

Oxidative stress is increasingly implicated in a number of neurodegenerative disorders characterized by abnormal filament accumulation in affected neurons, including Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. To further evaluate the role of oxidative stress in the neurodegenerative process and the accumulation of abnormal filaments, we examined the pathologic lesions in Pick disease and of corticobasal degeneration with immunocytochemistry by using antisera to heme oxygenase-1 (HO-1) - a putative marker of oxidative injury. Immunoreactivity to HO-1 was demonstrated in ballooned neurons, Pick bodies, neuropil threads, and glial inclusions (the latter two in a case of corticobasal degeneration). By immunoelectron microscopy, HO-1 immunolabelling of Pick bodies was closely associated with the abnormal filaments comprising the inclusion. Apparently unaffected neurons in all cases showed only background levels of HO-1 immunoreactivity. These data suggest that oxidative stress is important in the formation of the lesions characteristic of Pick disease and corticobasal degeneration. Moreover, taken together with our previous demonstration that HO-1 immunoreactivity is associated with the neurofibrillary pathology of Alzheimer disease, progressive supranuclear palsy, and subacute sclerosing panencephalitis, it appears that oxidative stress specifically targets the cytoskeleton in a variety of neurodegenerative disorders characterized by abnormal filament accumulation.
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PMID:Evidence for oxidative stress in Pick disease and corticobasal degeneration. 857 81

Central nervous system has a low antioxidative capacity, which is formed mainly by ascorbic acid. Therefore the cerebral tissue is threatened by the increased formation of free radicals and their metabolites (ROS--reactive oxygen species). ROS are formed such as in reperfusion phase after ischemia and in catecholamine metabolism, in oxidative stress due to hyperglycaemia. Polyunsaturated fatty acids (PUFA) are peroxidased by ROS; proteins and DNK are damaged as well. Free radicals are involved in etiology and pathogenesis of many CNS diseases, such as neuritis, Alzheimer disease, Parkinson disease, Huntington disease, aging and atherosclerosis of the brain, epilepsy, etc. During the antioxidant therapy it is necessary to consider the types of ROS, their origin and their mode of action, whether to administer hydrophilic or lipophilic antioxidants, eventually chelate agents, etc. Hydrophylic antioxidants are acting very soon after the administration, whereas the lipophilic ones reach their target tissues with a great delay. Therefore it is better to apply them preferentially like a prevention, if possible. Enzymatic antioxidants (SOD, GSPHx and catalase and others) are usually acting only for a short time. The methods of estimation of free radicals attacks are discussed as well their possible pathophysiological effects.
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PMID:[Free radicals in the central nervous system]. 866 12

The present studies assessed the levels of [125I][Sar1,ILE8]angiotensin II-labelled angiotensin AT1 and AT2 receptor recognition sites in homogenates of various brain areas (including caudate nucleus, putamen, substantia nigra, hippocampus, frontal cortex, temporal cortex and cerebellum) from patients with clinically diagnosed Parkinson's disease, Huntington's disease and Alzheimer's disease and those from age-, sex- and post-mortem delay-matched neurologically and psychiatrically normal patients. Radiolabelled angiotensin AT1 receptor recognition site levels were significantly decreased by approximately 70%, 70% and 90% in the caudate nucleus, putamen and substantia nigra, respectively, from patients with Parkinson's disease relative to matched controls. Furthermore, radiolabelled angiotensin AT2 receptor levels were decreased by some 60% in the caudate nucleus of patients with Parkinson's disease relative to control patients. In brain tissue homogenates from patients with Huntington's disease, the angiotensin AT1 receptor recognition site levels were decreased by approximately 30% in putamen relative to the control patients whilst angiotensin AT2 receptor levels were increased by some 90% in the caudate nucleus relative to the control patients. In brain tissue homogenates from patients with Alzheimer disease, the angiotensin AT2 receptor recognition site levels were significantly increased by approximately 200% in the temporal cortex relative to the control patients. The present results indicate that the reduction of angiotensin AT1 and/or AT2 receptor recognition site levels in the caudate nucleus, putamen and substantia nigra correlates with the principal neuropathology associated with Parkinson's disease and as such indicates that at least a significant population of angiotensin AT1 and AT2 receptors are located on the human dopaminergic nigrostriatal pathway. In addition, the marked increase in the levels of angiotensin AT2 receptor recognition sites in temporal cortex from patients with Alzheimer's disease correlates with some other markers associated with the renin-angiotensin system previously investigated in tissue from patients with this neurological disease.
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PMID:Alterations in angiotensin AT1 and AT2 receptor subtype levels in brain regions from patients with neurodegenerative disorders. 866 63

No therapy exists for the Lewy body diseases, which are an important cause of dementia. We regard Lewy body diseases and Parkinson disease as components of a spectrum of disorders having a degree of Alzheimer disease neuropathology. Immunologic features of Alzheimer disease and Parkinson disease suggest the involvement of similar phenomena in Lewy body diseases pathogenesis. Based on the efficacy of anti-inflammatory medication in arresting the progression of Alzheimer disease and the presence of common immunologic features in Alzheimer disease and Parkinson disease, a case is made for therapeutic intervention at the immune system level. Anti-inflammatory medications appear to be an appropriate therapeutic approach to Lewy body diseases.
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PMID:Lewy body diseases: possible new directions in prophylaxis and therapy. 867 55


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