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 present studies establish that there are specific, significant decreases in the neuronal calcium-binding protein (28-kDa calbindin-D) gene expression in aging and in neurodegenerative diseases. The specificity of the changes observed in calbindin mRNA levels was tested by reprobing blots with calmodulin, cyclophilin, and B-actin cDNAs. Gross brain regions of the aging rat exhibited specific, significant decreases (60-80%) in calbindin mRNA and protein levels in the cerebellum, corpus striatum, and brain-stem region but not in the cerebral cortex or hippocampus. Discrete areas of the aging human brain exhibited significant decreases (50-88%) in calbindin protein and mRNA in the cerebellum, corpus striatum, and nucleus basalis but not in the neocortex, hippocampus, amygdala, locus ceruleus, or nucleus raphe dorsalis. Comparison of diseased human brain tissue with age- and sex-matched controls yielded significant decreases (60-88%) in calbindin protein and mRNA in the substantia nigra (Parkinson disease), in the corpus striatum (Huntington disease), in the nucleus basalis (Alzheimer disease), and in the hippocampus and nucleus raphe dorsalis (Parkinson, Huntington, and Alzheimer diseases) but not in the cerebellum, neocortex, amygdala, or locus ceruleus. Since calbindin gene expression decreased specifically in brain areas known to be particularly affected in aging and in each of the neurodegenerative diseases, these findings suggest that decreased calbindin gene expression may lead to a failure of calcium buffering or intraneuronal calcium homeostasis, which contributes to calcium-mediated cytotoxic events during aging and in the pathogenesis of neurodegenerative diseases.
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PMID:Specific reduction of calcium-binding protein (28-kilodalton calbindin-D) gene expression in aging and neurodegenerative diseases. 214 Aug 97

The discovery of a specific association between nerve growth factor (NGF) and basal forebrain cholinergic neurons (BFCNs) marks the beginning of a new era of research into neurodegenerative diseases such as Alzheimer disease (AD). Degeneration of BFCNs appears to be one of the earliest and most prominent neuropathological features of a broad range of diseases of the human brain that give rise to loss of memory and dementia (including, in addition to Alzheimer disease, Parkinson disease, Lewy body dementia, progressive supranuclear palsy, dementia pugilistica, olivopontocerebellar atrophy, and Wernicke-Korsakoff syndrome). Selective localization of NGF receptors on BFCN, the relatively high levels of NGF mRNA in BFCN target areas, and numerous effects of exogenous NGF in vivo and in vitro provide overwhelming evidence that the structure and function of BFCNs in the adult brain are dependent on this molecule. The question then arises as to how this special relationship is disturbed in the diseased human brain? Initial investigations in AD have already indicated a normality of NGF mRNA and retention of receptors in the basal forebrain region. Interpretation of these results and the therapeutic relevance of NGF obviously depend upon future developments in understanding the role of NGF in the normal and pathological brain.
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PMID:Nerve growth factor and the basal forebrain cholinergic system: a link in the etiopathology of neurodegenerative dementias? 218 Apr 39

The prevalence of deposition of the Alzheimer's disease A4 amyloid protein in representative areas of the cerebral cortex was compared using a sensitive immunohistochemical technique in a group of 26 cases of idiopathic Parkinson's disease (PD) and in a control group of 82 subjects of comparable age who had died unexpectedly from non-cerebral causes. Cortical A4 protein deposition was found in 54% of PD subjects and 48% of the control group, while deposition of A4 protein in meningeal or cortical blood vessels was found in 38% of PD subjects and 25% of controls. When allowance was made for age and sex, the differences between the two groups were not found to be statistically significant. Heavy cortical A4 protein deposition was found in a number of PD cases, including two of four cases with dementia, and was absent in the other two cases. The present findings indicate that a large proportion of cases of idiopathic PD have associated Alzheimer's disease changes. In some cases these lesions are of sufficient severity to account for dementia. In other cases the changes are less severe and are probably subclinical but may be a contributory factor to the development of cognitive impairment and dementia. The absence of Alzheimer changes in some demented PD cases indicates that the dementia of PD is heterogeneous.
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PMID:Deposition of Alzheimer's disease amyloid (A4) protein in the cerebral cortex in Parkinson's disease. 269 Jan 9

Several degenerative diseases of the nervous system are characterized by the presence of neuronal inclusions. Most of these inclusions are made of abnormal filaments and share epitopes with cytoskeletal proteins. One of these inclusions, the neurofibrillary tangle of Alzheimer disease, has recently been shown to contain ubiquitin, a regulatory protein thought to play a role in the degradation of abnormal proteins. We carried out light and electron microscopic immunocytochemistry with several polyclonal and monoclonal antibodies to investigate the presence of ubiquitin in neuronal inclusions of neurodegenerative diseases. Ubiquitin was present not only in paired helical filaments that form the neurofibrillary tangle of Alzheimer disease, but also in the filamentous components of the inclusion characteristic of Parkinson disease, Pick disease, and progressive supranuclear palsy. In contrast, ubiquitin was not detected in other neuronal inclusions often found in aging and in Alzheimer disease, such as Hirano bodies and granulovacuolar degeneration. Reactivity with monoclonal antibodies suggests differences in the ubiquitin-acceptor proteins present in the inclusions studied. It is concluded that ubiquitin is selectively present in neuronal inclusions of degenerative diseases.
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PMID:Ubiquitin is associated with abnormal cytoplasmic filaments characteristic of neurodegenerative diseases. 283 68

Although patients with Alzheimer disease have a well-demonstrated deficit in cortical cholinergic markers, treatments designed to enhance cholinergic activity in the central nervous system have not achieved the clinical success of dopamine replacement for Parkinson disease. A brief review of recent clinical reports and some developments in the neurosciences suggests that it may be premature, however, to abandon the search for benefit from cholinergic enhancement therapy in Alzheimer disease.
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PMID:Update on cholinergic enhancement therapy for Alzheimer disease. 333 48

In the brains of humans and other mammals, there are two principal groups of cholinergic nuclei aside from those forming the cranial motor nuclei. One group lies in the forebrain and includes the nucleus basalis of Meynert. The second group lies in the hindbrain and includes the nucleus tegmenti pedunculopontinus (NPP), identified by Mesulam et al. [Mesulam, M.-M., Mufson, E. J., Wainer, B. H. & Levey, A. I. (1983) Neuroscience 10, 1185-1201] as cholinergic cell group Ch5. The basal forebrain cholinergic cell groups, which innervate widespread areas of the neocortex, undergo degeneration in Alzheimer disease and also in parkinsonism associated with dementia. We here report that the hindbrain NPP Ch5 cell group, thought to innervate many nuclei of the extrapyramidal motor system, the superior colliculus, and the substantia innominata, undergoes degeneration in idiopathic Parkinson disease and in the parkinsonian syndrome of progressive supranuclear palsy. These findings strongly suggest that degeneration in the brainstem in Parkinson disease is not confined to catecholamine-containing neurons, but that cholinergic neurons of the NPP are also vulnerable. The findings further raise the possibility that certain symptoms of Parkinson disease and progressive supranuclear palsy have their genesis in pathology of these cholinergic neurons.
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PMID:Neuronal loss in the pedunculopontine tegmental nucleus in Parkinson disease and in progressive supranuclear palsy. 347 16

The causes of amyotrophic lateral sclerosis, Parkinson disease, and Alzheimer disease are unknown. Furthermore, treatment for two of these conditions is almost totally lacking. The thesis is presented that each of these disorders is due to lack of a disorder-specific neurotrophic hormone. The hormone would be elaborated or stored in the target of the affected neurons. It would be released by the postsynaptic cell and then exert its effects in a retrograde fashion after being taken up by the presynaptic terminal. In the lower motor neuron syndromes of amyotrophic lateral sclerosis, failure of muscle cells to release the appropriate motor neurotrophic hormone would result in impaired function of anterior horn cells. In Parkinson disease, the neurotrophic failure would be characterized by inability of striatal cells to provide the required dopamine neurotrophic hormone with resulting impairment of substantia nigra cells. In Alzheimer disease, the abnormalities would lie in failure of the hippocampus and cortical cells to supply the relevant cholinergic neurotrophic hormone with resulting impairment of medial septal and nucleus basalis neurons. Central nervous system tissue culture provides a convenient system in which to assay these neurotrophic hormones and should permit a test of the hypothesis.
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PMID:A unifying hypothesis for the cause of amyotrophic lateral sclerosis, parkinsonism, and Alzheimer disease. 617 10

Graphite furnace atomic-absorption spectroscopy was used to measure aluminum concentrations in brain samples from 33 patients dying from a variety of neurologic diseases. Four samples from patients dying of nonneurologic causes also were studied. Nine samples (one from each of nine patients) of Creutzfeldt-Jakob disease brain contained normal amounts of aluminum. Aluminum was increased in 9 of 18 brain specimens with seven different pathologic processes. This included three of seven Alzheimer disease, two of three Huntington disease, two of two Parkinson disease, one of one progressive supranuclear palsy, one of one acoustic neuroma, one of two cerebrovascular disease, and one of two Guamanian amyotrophic lateral sclerosis (ALS). Aluminum was normal in the remaining samples (four normal, two ALS, one multiple sclerosis, one Pick disease, and two Guamanian parkinsonism-dementia). The significance of high aluminum values is not clear, but the normal values from the Creutzfeldt-Jakob cases imply that neuronal destruction per se need not lead to accumulation of aluminum in the brain.
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PMID:Brain destruction alone does not elevate brain aluminum. 645 8

Reductions in the numbers of binding sites for the serotonergic S2-receptor antagonist, ketanserin, are, as previously reported, evident in Alzheimer's disease. New findings indicate that these sites are not affected in the cortex of patients with Parkinson's disease despite the presence of cognitive impairment. In contrast S1-receptor binding sites were reduced to a small but significant extent in both Alzheimer's and Parkinson's disease with cognitive deficit. The S2-receptor binding loss was not related to the cholinergic deficit (decreased choline acetyltransferase) common to both disorders nor to the presence of cortical senile plaques but did relate to the extent of cortical neurofibrillary tangle formation, evident in Alzheimer's but not generally in Parkinson's disease. These observations suggest that S2- but not S1-receptor binding abnormalities may reflect an important intrinsic cortical involvement specifically associated with the Alzheimer disease process.
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PMID:Cortical serotonin-S2 receptor binding abnormalities in patients with Alzheimer's disease: comparisons with Parkinson's disease. 652 62

Demented patients with Parkinson disease share certain neuropathological and neurochemical features with patients suffering from Alzheimer disease. Recently, loss of cholinergic neurons in the basal forebrain, particularly the nucleus basalis of Meynert, has been implicated in the pathophysiology of Alzheimer disease. The present investigations of 12 patients with Parkinson disease demonstrates that the demented patients with this disease also show a selective loss of cells in the nucleus basalis of Meynert, thus providing an important link between the dementias of Alzheimer disease and Parkinson disease.
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PMID:Basal forebrain neurons in the dementia of Parkinson disease. 684 36


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