Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autopsy material of 13 persons who died between 70 and 89 yrs old and of patients who died between 27 and 44 yrs old was studied. White matter of temporal, parietal, and occipital lobes was investigated using histological and biochemical methods. According to results of neuropathological studies, the material of aged patients was divided into two subgroups: (a) brains with vascular changes only and (b) patients with senile atrophy of Alzheimer type. Chemical changes found in all studied brain lobes included a mild decrease in Wolfgram protein content with reciprocal increase in large basic protein content, together with a marked decrease in myelin yield. The abovementioned chemical changes were almost identical whether they were only vascular changes or whether senile atrophy of Alzheimer type was also present. It seems, therefore, that the degeneration of vessels is the decisive factor in the pathogenetic mechanism of myelin lesions in the aged brain.
Mol Chem Neuropathol 1991 Feb
PMID:Myelin proteins in aging human brain. 191 Mar 53

In Parkinson's disease (PD), in addition to degeneration of the nigrostriatal dopaminergic pathway, a variety of neuronal systems are involved, causing multiple neuromediator dysfunctions that account for the complex patterns of functional deficits. Degeneration affects the dopaminergic mesocorticolimbic system, the noradrenergic locus ceruleus (oral parts) and motor vagal nucleus, the serotonergic raphe nuclei, the cholinergic nucleus basalis of Meynert, pedunculopontine nucleus pars compacta, Westphal-Edinger nucleus, and many peptidergic brainstem nuclei. Cell losses in subcortical projection nuclei range from 30 to 90% of controls; they are more severe in depressed and demented PD patients. Most of the lesions are region-specific, affecting not all neurons containing a specific transmitter or harboring Lewy bodies. In contrast to Alzheimer's disease (AD), subcortical system lesions in Parkinson's disease appear not to be related to cortical pathology, suggesting independent or concomitant degeneration. The pathogenesis of multiple-system changes contributing to chemical pathology and clinical course of Parkinson's disease are unknown.
Mol Chem Neuropathol 1991 Jun
PMID:Pathology of Parkinson's disease. Changes other than the nigrostriatal pathway. 195 62

Human brain levels of glutathione (GSH), glutathione disulfide (GSSG), and vitamin E were measured in neurologically normal control patients and two groups of patients with neurodegeneration: those with Alzheimer's disease (AD), and AD with some features of Parkinson's disease (AD-PD). Control brain samples contained GSH levels more than 50 times higher than GSSG. The levels of GSH were highest in the caudate nucleus and lowest in the medulla. In patients with AD or AD-PD, hippocampal levels of GSH were significantly higher than controls. Patients with AD also demonstrated high GSH levels in the midbrain compared to normal. In contrast, patients with AD-PD did not have significantly elevated GSH levels in this site. GSSG levels were not significantly different in any brain region between controls and diseased patients. In control brains, the medulla had higher levels of vitamin E than any other brain region. The caudate nucleus had the lowest levels, which were about half the levels in the medulla. Control levels of vitamin E in the midbrain were about 18.8 micrograms/g. In AD patients the midbrain levels of vitamin E doubled to 42.3 micrograms/g. This doubling also occurred in AD-PD patients where midbrain vitamin E levels increased to 44.0 micrograms/g. These results may indicate that compensatory increases in GSH and vitamin E levels occur following damage to specific brain regions in patients with AD or AD-PD.
Mol Chem Neuropathol 1991 Jun
PMID:Alzheimer's and Parkinson's disease. Brain levels of glutathione, glutathione disulfide, and vitamin E. 195 64

From a chromosome 21 phage library, we selected 10 clones located proximal of the senile plaque amyloid precursor protein gene. Since a locus for Alzheimer's disease (AD) has been localized in the pericentromeric region of chromosome 21, the selected phage clones are potential candidate probes for genetic analysis of AD. In this study, we subcloned single-copy fragments of the selected phage clones, refined their physical localization, and examined their chromosomal distribution in relation to their position on chromosome 21. The results indicated that the phage clones are identifying nine chromosome 21 loci, which, if polymorphic, may be helpful in localizing the AD locus more precisely. Moreover, since all phage clones are located close to the centromere of chromosome 21, they can be used to determine the parental origin of nondisjunction in trisomy 21 with high reliability.
Somat Cell Mol Genet 1990 May
PMID:Physical mapping of chromosome 21 DNA markers in Alzheimer's disease region using somatic cell hybrids. 197 17

The deposition of amyloid beta A4 in the brain is a major pathological hallmark of Alzheimer's disease. Amyloid beta A4 is a peptide composed of 42 or 43 amino acid residues. In brain, it appears in the form of highly insoluble, filamentous aggregates. Using synthetic peptides corresponding to the natural beta A4 sequence as well as analog peptides, we demonstrate requirements for filament formation in vitro. We also determine aggregational properties and the secondary structure of beta A4. A comparison of amino-terminally truncated beta A4 peptides identifies a peptide spanning residues 10 to 43 as a prototype for amyloid beta A4. Infrared spectroscopy of beta A4 peptides in the solid state shows that their secondary structure consists of a beta-turn flanked by two strands of antiparallel beta-pleated sheet. Analog peptides containing a disulfide bridge were designed to stabilize different putative beta-turn positions. Limited proteolysis of these analogs allowed a localization of the central beta-turn at residues 26 to 29 of the entire sequence. Purified beta A4 peptides are soluble in water. Size-exclusion chromatography shows that they form dimers that, according to circular dichroism spectroscopy, adopt a beta-sheet conformation. Upon addition of salts, the bulk fraction of peptides precipitates and adopts a beta-sheet structure. Only a small fraction of peptides remains solubilized. They are monomeric and adopt a random coil conformation. This suggests that the formation of aggregates depends upon a hydrophobic effect that leads to intra- and intermolecular interactions between hydrophobic parts of the beta A4 sequence. This model is sustained by the properties of beta A4 analogs in which hydrophobic residues were substituted. These peptides show a markedly increased solubility in salt solutions and have lost the ability to form filaments. In contrast, the substitution of hydrophilic residues leads only to small deviations in the shape of filaments, indicating that hydrophilic residues contribute to the specificity of interactions between beta A4 peptides.
J Mol Biol 1991 Mar 05
PMID:Aggregation and secondary structure of synthetic amyloid beta A4 peptides of Alzheimer's disease. 200 99

1. Amyloid plaques found in the brains of Alzheimer's diseased patients are composed of the 42 amino acid beta-amyloid peptide (BAP) which is processed out of the larger amyloid precursor protein (APP). 2. To study the regulation of the APP gene expression, we have isolated the promoter region of this angle of this single-copy gene and produced a reporter gene system to determine if the promoter is responsive to agents that may cause the overproduction of APP leading to the abnormal accumulation of plaques in AD. 3. The promoter contains sequences homologous to heat shock elements, AP-1 binding sites, and phorbol ester-inducible sequences as well as GG-rich regions found in other constitutively expressed genes. 4. We show here that this promoter is inducible in cultured cells by interleukin-1 (IL-1) in a transient assay system and that the HSE and AP-1 binding site are required for this inducibility. 5. This induction of transcription from the APP promoter implies that this gene is responsive to tropic and/or trophic agents which may be present in the diseased brain.
Cell Mol Neurobiol 1990 Dec
PMID:Interleukin-1 stimulates the beta-amyloid precursor protein promoter. 209 32

We have previously shown that sera from patients with Alzheimer's disease (AD) contain antibodies to the cell bodies (perikarya; PK) of purely cholinergic Torpedo neurons, and that repeated immunization of rats with this neuronal preparation for over a year induces learning and memory impairments. In the present study, we examined the brain morphology of cholinergic PK immunized rats relative to controls. Immunohistochemical studies of the brains of these rats revealed the accumulation of IgG in specific areas, such as, the hippocampus. Parallel histochemical studies demonstrated significant changes in the hippocampus, and in white matter areas. They included large vacuoles and necrotic nuclei in the granular layer of the dentate gyrus, tangle-like appearance in some pyramidal neurons of the hippocampus, and vacuolar degeneration accompanied by oligodendroglia hypertrophy in white matter tracts, such as, the corpus callosum and fimbria. In contrast, immunization with Torpedo cholinergic nerve terminals, that has no cognitive effects on the rat, also did not induce brain morphological changes. These findings suggest that the learning and memory deficits induced by immunizing rats with cholinergic PK are related to the observed brain morphological changes, and support the hypothesis that the antibodies to cholinergic neurons found in the sera of AD patients may play a role in neuronal degeneration in this disease.
Mol Chem Neuropathol
PMID:Immunization with cholinergic cell bodies induces histopathological changes in rat brains. 209 84

Based on recent studies of neuroimmune networks, the lymphocyte binding of serotonin neurotransmitter was studied in patients with Alzheimer's disease, idiopathic mental retardation, and autism. The specific binding to lymphocytes of [3H]serotonin, at a single concentration of 100 nM, was significantly reduced in Alzheimer's disease patients as compared to aged controls (group mean of 3.667 +/- 2.301 v 7.506 +/- 1.717 picomoles; p = 0.001), and in children with idiopathic mental retardation as compared to healthy children (group mean of 3.694 +/- 1.627 v 5.792 +/- 1.902 picomoles; p = 0.003). However, autistic children did not differ significantly from the healthy children (group mean of 5.287 +/- 1.987 v 5.792 +/- 1.902 picomoles; p = 0.475). Reduced lymphocyte binding of serotonin may be an indication of breakdown of an unknown neuroimmune pathway relevant to the pathophysiology of Alzheimer's disease and idiopathic mental retardation.
Mol Chem Neuropathol 1990 Dec
PMID:Binding of [3H]serotonin to lymphocytes in patients with neuropsychiatric disorders. 209 81

1. Abundant senile plaques and neurofibrillary tangles in certain brain regions constitute the major neuropathological characteristics of Alzheimer's disease. Recent work has established that the amyloid beta protein, which is derived from a large precursor, constitutes the major constituent of plaque amyloid, whereas the microtubule-associated protein tau is a component of the paired helical filament, the major constituent of neurofibrillary tangles. 2. Multiple isoforms of amyloid beta protein precursor and tau protein are produced from a single gene through alternative RNA splicing. By Northern blotting amyloid beta protein precursor transcripts are found throughout central and peripheral tissues, whereas tau protein transcripts are only found in the nervous system. 3. In the central nervous system the cellular localization of amyloid beta protein precursor and tau protein transcripts is neuronal. The cells affected in Alzheimer's disease patients produce both types of transcripts; however, the various transcripts are also found in cells not affected in the course of the disease. At present, there exists no evidence to suggest that an overproduction of amyloid beta protein precursor or tau protein is the reason for plaque and tangle formation. The formation of the latter probably results from posttranslational events.
Cell Mol Neurobiol 1990 Mar
PMID:Molecular neuropathology of Alzheimer's disease: in situ hybridization studies. 211 May 5

Studies were undertaken on the processing of Alzheimer's disease-associated beta-amyloid precursor protein in normal cultured human fibroblasts and a human neuroblastoma cell line. Major differences in processing between the secreted and intracellular forms of the precursor were found. The intracellular form appears to undergo amino-terminal processing yielding many smaller fragments, whereas the secreted form does not show any further proteolytic cleavage after its release from the cell surface. In pulse-chase experiments, antibodies to the A4 region immunoprecipitated bands of Mr = 92,000-128,000, which represent the intact precursor; several smaller intracellular fragments of Mr = 70,000-72,000, 55,000, 33,000 and 6,000 also immunoprecipitated with this antibody. The Mr = 6,000 band cleared from the cell very quickly and is postulated to be the A4-carrying remnant of the secreted protein. The data show that a fragment of Mr = 33,000, which includes the A4 region, is one stable processed end-product of the intracellular precursor protein. It is possible that different posttranslational modifications are the signals responsible for the differences in processing between the secreted and intracellular amyloid precursor protein.
J Mol Neurosci 1990
PMID:Processing of Alzheimer's disease-associated beta-amyloid precursor protein. 212 35


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>