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)

Ubiquitin-positive Lewy neurites and Lewy bodies are found in idiopathic Parkinson's disease (PD) and diffuse Lewy body disease (DLBD). We found that, in three patients with PD and one with DLBD, microtubule-associated protein 5 (MAP5) immunostaining was consistently present in both Lewy neurites and Lewy bodies throughout the brainstem and forebrain regions affected in the disease. In contrast, other cytoskeletal markers (neurofilaments and MAP2) could be demonstrated in only a small fraction of Lewy bodies and neurites. Confocal microscopy demonstrated that MAP5 immunolabeling was located around the perimeter of the ubiquitin-positive labeling which occupied the central region of the neurite and Lewy body, with some overlap between MAP5 and ubiquitin staining. In contrast, in those Lewy bodies and neurites immunopositive for phosphorylated and non-phosphorylated neurofilament proteins, the neurofilament labeling was quite peripheral to the ubiquitin staining, with little or no overlap. Our results suggest MAP5 is more closely associated with the ubiquitinated proteins of Lewy bodies and neurites than other cytoskeletal proteins.
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PMID:Microtubule-associated protein 5 is a component of Lewy bodies and Lewy neurites in the brainstem and forebrain regions affected in Parkinson's disease. 877 50

Clinical criteria for dementia with Lewy bodies (DLB) have been proposed, but their formulation, reliability, and validity require further study. Pathologic criteria for DLB are also undergoing evolution. Two studies were conducted with the goal of identifying the components of these evolving criteria that may benefit from further refinement; one study evaluated the components of the clinical criteria and another study operationalized the pathologic criteria for DLB. Twenty-four patients with a premorbid diagnosis of probable or possible Alzheimer's disease (AD) (n = 18), Parkinson's disease (PD) (n = 5), or progressive supranuclear palsy (PSP) (n = 1) were studied. Inter-rater reliability and validity of the clinical criteria were determined by a retrospective chart review, done by five neurologists, and a blinded pathologic evaluation. The Consortium on dementia with Lewy bodies (CDLB) pathologic criteria were operationalized to compare past criteria and test the validity of the evolving clinical criteria on the dementia patients. Three or more cortical fields (at 250 x magnification) with many (four or more) Lewy bodies (LBs) on ubiquitin immunoreactive sections were required to meet the CDLB neocortical score of > 6. Fifteen of the AD patients had at least one LB in a cortical section, four had many LBs, while three had no LBs; all patients with movement disorder had at least one LB in a cortical section. The sensitivity/specificity ratio of the CDLB probable DLB clinical criteria based upon many LBs being present was 75%/79%. Reformulated clinical criteria that require the presence of extrapyramidal signs significantly predicted those patients with many LBs versus those with few or no LBs (chi 2 = 5.48, p = 0.02) and increased clinical specificity to 100%. This preliminary study identifies components of the evolving clinical and pathologic criteria for DLB that require further refinement.
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PMID:Dementia with Lewy bodies: reliability and validity of clinical and pathologic criteria. 896 Jul 18

To determine at the tissue level whether the proteasome (Ps), a unique nonlysosomal protease, is involved in the metabolism of ubiquitinated proteins, we examined for the first time the immunocytochemical localizations of both Ps and ubiquitin (Ub) in sections of various abnormal structures that are known to be ubiquitinated in various neurodegenerative diseases and in the elderly. Concomitant increases of Ps and Ub were observed at the sites of most dystrophic neurites in Alzheimer disease (AD) and parkinsonism-dementia complex on Guam (PDC) and in Lewy bodies in Parkinson's disease and diffuse Lewy body disease, but not in neurofibrillary tangles in AD or PDC, in filamentous inclusions within anterior horn cells in sporadic motor neuron disease, or in eosinophilic granules in the olivary nucleus of the elderly. These results at the tissue level indicated that Ps is involved in the metabolism of some, but not all, ubiquitinated proteins and structures in various neurodegenerative disorders. This suggests that the involvement of Ps in the metabolism of ubiquitinated structures differs in different cases and at different stages of disease. These results and our previous immunocytochemical studies of lysosomal cathepsin proteases suggest that both nonlysosomal and lysosomal systems are involved in the metabolism of various ubiquitinated proteins and that their involvements differ in different structures and at different stages of degeneration of the structures.
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PMID:Immunocytochemical co-localization of the proteasome in ubiquitinated structures in neurodegenerative diseases and the elderly. 903 65

Genetic influences are thought by many to play an important role in the cause of Parkinson's disease. We studied two closely intermarried families (Family G) whose ancestors immigrated to the United States from Russia. We investigated this family clinically, genealogically, and pathologically. Our pedigree contained 102 members spanning six generations, with 10 affected individuals and 1 affected spouse. Detailed telephone interviews were conducted with affected individuals, with their spouses, and with their at-risk siblings. Medical records of deceased and living affected patients were collected. Physical examinations were performed on 7 at-risk and 5 affected persons. Typical levodopa-responsive parkinsonism with bradykinesia, rigidity, resting tremor, and impaired postural reflexes was seen in 4 members, dementia was present in 3, and 3 had both dementia and parkinsonism. An autopsy completed on 1 individual, our index case, demonstrated Lewy bodies in the brainstem and neocortex and ubiquitin-positive neuritic degeneration in the CA2-3 region of the hippocampus, consistent with the limbic (transitional) form of Lewy body disease. This family is distinct both clinically and pathologically from several previously reported parkinsonian kindreds.
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PMID:Familial parkinsonism, dementia, and Lewy body disease: study of family G. 938 76

Neuronal degeneration occurs in the substantia nigra pars compacta (SNpc) of patients with Parkinson's disease and other Lewy body-associated disorders. Lewy bodies (LBs) are abnormal inclusions found in the SNpc and other neurons of these patients. It is not known what role LBs play in the disease process; they may be harmful to the neuron or simply an epiphenomenon of the disease process. We have previously shown that some of the neuronal death occurring in the SNpc of Lewy body-associated disorders resembles apoptosis. The present study was undertaken to determine whether apoptotic-like changes were more common in SNpc neurons with somal LBs compared to those without somal LBs. Substantia nigra from cases of Lewy body-associated disorders were labeled to colocalize apoptotic-like changes and LBs using in situ end-labeling and an anti-ubiquitin antibody. Three cases demonstrated that SNpc neurons with LBs in the perikarya had the same proportion of apoptotic-like changes as SNpc neurons without somal LBs. One case had no LB-containing SNpc neurons undergoing apoptotic-like cell death. The majority of SNpc neurons undergoing apoptotic-like cell death did not appear to contain somal LBs and thus may be dying before LB formation can occur. These results support the theory that the presence of a somal LB does not predispose a neuron to undergo apoptotic-like cell death.
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PMID:Contribution of somal Lewy bodies to neuronal death. 943 24

Double-labelling immunohistochemistry of Bcl-2 and Bax, and ubiquitin (as a marker of Lewy bodies) was examined in the brains of patients with Parkinson's disease and Diffuse Lewy body disease to learn about possible modifications of protein expression and the presence of Lewy bodies. Bcl-2 and Bax immunoreactivities were observed in Lewy body-bearing and non-Lewy body-bearing neurons in patients with parkinsonism. These results show that Bcl-2 and Bax are probably not implicated in Lewy body formation and that the presence of Lewy bodies does not have a direct impact on the expression of Bcl-2 and Bax proteins in individual neurons.
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PMID:Bcl-2 and Bax proteins in Lewy bodies from patients with Parkinson's disease and Diffuse Lewy body disease. 946 59

The precursor of the non-Abeta component of Alzheimer's disease amyloid (NACP) (also known as a-synuclein) is a presynaptic terminal molecule that accumulates in the plaques of Alzheimer's disease. Recent studies have shown that a mutation in NACP is associated with familial Parkinson's disease, and that Lewy bodies are immunoreactive with antibodies against this molecule. To clarify the patterns of accumulation and differences in abnormal compartmentalization, we studied NACP immunoreactivity using double immunolabeling and laser scanning confocal microscopy in the cortex of patients with various neurodegenerative disorders. In Lewy body variant of Alzheimer's disease, diffuse Lewy body disease, and Parkinson's disease, NACP was found to immunolabel cortical Lewy bodies, abnormal neurites, and dystrophic neurites in the plaques. Double-labeling studies showed that all three of these neuropathological structures also contained ubiquitin, synaptophysin, and neurofilament (but not tau) immunoreactivity. In contrast, neurofibrillary tangles, neuropil threads, Pick bodies, ballooned neurons, and glial tangles (most of which were tau positive) were NACP negative. These results support the view that NACP specifically accumulates in diseases related to Lewy bodies such as Lewy body variant of Alzheimer's disease, diffuse Lewy body disease, and Parkinson's disease and suggests a role for this synaptic protein in the pathogenesis of neurodegeneration.
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PMID:Abnormal accumulation of NACP/alpha-synuclein in neurodegenerative disorders. 946 62

NACP, originally identified as a precursor of the non-Abeta component of Alzheimer's disease amyloid (NAC), is now known to be identical to alpha-synuclein, a presynaptic protein in the human brain. Recently, a mutation in the alpha-synuclein gene in families with autosomal dominant Parkinson's disease (PD) was identified. We carried out immunohistochemical examinations of the brains of sporadic PD patients using anti-NACP and anti-ubiquitin antibodies. Consistent with previous studies, the anti-NACP antibody immunostained the neuropil in a punctate pattern throughout the brain. Moreover, much stronger NACP immunoreactivity was found in Lewy bodies and degenerating neurites in the brainstem. Serial sections immunolabeled with anti-ubiquitin or anti-NACP showed that all ubiquitin-immunoreactive LBs were also NACP-immunoreactive. These findings suggest that alteration of NACP metabolism is involved in the pathogenesis of PD, particularly in Lewy body formation, leading to neurodegeneration.
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PMID:NACP, a presynaptic protein, immunoreactivity in Lewy bodies in Parkinson's disease. 954 68

Parkinson's disease is a common neurodegenerative disease with complex clinical features. Autosomal recessive juvenile parkinsonism (AR-JP) maps to the long arm of chromosome 6 (6q25.2-q27) and is linked strongly to the markers D6S305 and D6S253; the former is deleted in one Japanese AR-JP patient. By positional cloning within this microdeletion, we have now isolated a complementary DNA done of 2,960 base pairs with a 1,395-base-pair open reading frame, encoding a protein of 465 amino acids with moderate similarity to ubiquitin at the amino terminus and a RING-finger motif at the carboxy terminus. The gene spans more than 500 kilobases and has 12 exons, five of which (exons 3-7) are deleted in the patient. Four other AR-JP patients from three unrelated families have a deletion affecting exon 4 alone. A 4.5-kilobase transcript that is expressed in many human tissues but is abundant in the brain, including the substantia nigra, is shorter in brain tissue from one of the groups of exon-4-deleted patients. Mutations in the newly identified gene appear to be responsible for the pathogenesis of AR-JP, and we have therefore named the protein product 'Parkin'.
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PMID:Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. 956 Jan 45

Lewy body disease (LBD) is a progressive neurological disorder with parkinsonism, having many Lewy bodies (LBs) and degenerative changes. LBD is classified into the three types according to the distribution of LBs: "brain-stem type", "transitional type" and "diffuse type". The brain-stem type is identical to classical Parkinson's disease (PD). The diffuse type is nominated as "diffuse Lewy body disease" (DLBD). DLBD is a neuropathological entity, characterized by abundant LBs not only in the basal ganglia and brain-stem but in the cerebral cortex, combined with senile changes. Juvenile onset DLBD is called "pure form" of DLBD because of no or few senile changes. The LBs are present in the amygdala, nucleus basalis of Meynert, hypothalamic nuclei, substantia nigra, nucleus paranigralis, locus caeruleus, dorsal vagal nucleus and reticular nuclei. The cerebral LBs are numerous in the parahippocampal gyrus, cingular gyrus, and insular, frontal and temporal cortices. The LBs show immunoreactivity to ubiquitin and the ubiquitin-immunoreactive neurites in the CA2-3 region appear to be specific for DLBD. The clinical features of DLBD in the senium are progressive dementia, psychotic state, parkinsonism and autonomic signs. In general, progressive dementia is an initial symptom, followed by parkinsonism in the later stage. Some show progressive autonomic failure. A few present respiratory failure or vocal cord palsy resulting in sudden death in DLBD. DLBD is characterized neurochemically by severe affection of multiple neurotransmitters networks. In DLBD an impairment of the innominato-cortical cholinergic and mesocortical dopaminergic system, differentiating from Alzheimer's disease and PD, may play an important role in developing disease process.
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PMID:[Diffuse Lewy body disease]. 957 69


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