Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alzheimer's disease is a frequent cause of dementia in the elderly. The prevalence and incidence increase with aging. It is hypothesised that the age related decline in liver size and lysosomal function results in decreased clearance as well as decreased or altered proteolysis of the Alzheimer precursor protein, and results in the deposition of A4 protein in cerebral blood vessels and brain with congophilic angiopathy and senile/amyloid plaque formation.
 ...
PMID:Hepatic aging as an etiological factor in the development of Alzheimer's disease. 229 79

Brains of patients with Alzheimer disease/senile dementia of Alzheimer type (AD/SDAT) develop a progressive accumulation of amyloid, which deposits primarily in the form of characteristic parenchymal 'plaques' (senile or neuritic plaques/SP's) and as mural deposits in the walls of capillaries and arterioles (cerebral amyloid angiopathy /CAA). A major component of this amyloid is a small and unique peptide composed of 39-43 amino acids, beta/A4, which is cleaved from a much larger precursor protein (APP) that has several isoforms. Brain amyloid can be detected in autopsy or biopsy brain tissue by classical, immunohistochemical and ultrastructural (including immuno-electron microscopic) methods of varying sensitivity and specificity. Beta/A4 amyloid deposition is remarkably variable (e.g. predominantly parenchymal or vascular, or a mixture of parenchymal and vascular) among patients with AD/SDAT. Despite its abundance in the brains of AD/SDAT patients, the precise role of beta/A4 in the pathogenesis of the neurological deficit, neocortical atrophy and progressive synapse loss associated with AD/SDAT has yet to be determined. However, mutations in the gene that encodes APP are clearly associated with familial AD syndromes in which there is significant brain amyloid deposition. CAA, in addition to its association with AD/SDAT, can result in hemorrhagic and (possibly) ischemic forms of stroke. Work with recently developed transgenic mice which express large amounts of beta/A4 in the central nervous system is likely to elucidate mechanisms by which the protein is selectively or deposited in the brain in a parenchymal or microvascular form, and how it contributes to the pathogenesis of neurodegeneration.
 ...
PMID:Brain parenchymal and microvascular amyloid in Alzheimer's disease. 873 32

The cerebral amyloid angiopathies comprise a heterogeneous group of disorders that are characterized clinically by ischaemic and/or haemorrhagic strokes, and histologically by deposition of amyloid in the wall of leptomeningeal and cerebral cortical blood vessels. On the basis of the molecular composition of the amyloid, two forms can be distinguished. Cystatin C amyloid angiopathy is a rare autosomal dominant disorder confined to several families from Iceland. beta-amyloid cerebral amyloid angiopathies may be hereditary or sporadic, and share clinical, pathological and biochemical features with Alzheimer's disease. Both types of vascular amyloid derive from precursor proteins synthesized in situ by astrocytes (cystatin C) or smooth muscle cells (beta-amyloid), and induce progressive degeneration of smooth muscle cells, blood vessel rupture and haemodynamic changes. In recent years, it has been reported that mutations underlying both types of hereditary cerebral amyloid angiopathy directly involve the gene encoding the precursor protein. These findings have increased our understanding of the amyloidogenic mechanisms and allowed preclinical diagnosis. Nevertheless, the aetiopathogenetic factors involved in the more frequent sporadic form of amyloid angiopathy remain unknown.
 ...
PMID:Cerebral amyloid angiopathies. 880 23

In this study, we immunohistochemically examined the several constituents of senile plaques (SPs) and cerebral amyloid angiopathy (CAA) in aged cynomolgus monkeys. Apolipoprotein E (apoE) deposited in all mature plaques and CAA, and in half of the diffuse plaques. Alpha-1-antichymotripsin (alpha ACT) deposited in half of the mature plaques and in one third of the CAA. Amyloid precursor protein (APP), ubiquitin (Ub), and microtubule-associated protein-2 (MAP-2) accumulated in the swollen neurites of mature plaques. Glial fibrillary acidic protein (GFAP) was detected in the astrocytes and their processes surrounding the mature plaques. Tau was detected in neither the SPs nor CAA. Therefore, mature plaques involved extracellular A beta, apoE, and alpha ACT, and also astrocytes and swollen neurites. However, diffuse plaques involved only extracellular A beta and apoE. Since these features, except for tau, were consistent with those in humans, this animal model will be useful for studying the pathogenesis of cerebral amyloid deposition.
 ...
PMID:Immunohistochemical characteristics of the constituents of senile plaques and amyloid angiopathy in aged cynomolgus monkeys. 890 9

Smooth muscle cells cultured from leptomeningeal vessels from old dogs with amyloid-angiopathy accumulate intracellular deposits that are immunoreactive for amyloid-beta peptide (A beta). We used this cellular model in the present study to examine the influence of sera and cerebrospinal fluid on intracellular accumulation of A beta-immunoreactive deposits and on secretion of soluble A beta into culture media. We found that sera from old dogs significantly increased the percentage of A beta-positive smooth muscle cells in culture. The enhanced accumulation of A beta was associated with (a) lower secretion of A beta into media, (b) altered maturation of amyloid-beta-precursor protein (A betaPP) into A betaPP751-770 with faster electrophoretic mobility, (c) increased accumulation of C-terminal fragments of A betaPP (12-15 kD, 10kD and less), and (d) increased secretion of A betaPP into culture media. These findings suggest that age- or disease-related serum factors increase accumulation of A beta by affecting production and processing of A betaPP In contrast, cerebrospinal fluids reduced accumulation of A beta. Involvement of A beta-carrier proteins-apolipoprotein E and transthyretin-in accumulation of A beta is demonstrated. Accumulation of A beta in cultured smooth muscle cells-a model of beta-amyloidosis-may be regulated by factors that alter production and processing of A betaPP as well as the fate of soluble A beta in extracellular space.
 ...
PMID:Accumulation of Alzheimer amyloid-beta peptide in cultured myocytes is enhanced by serum and reduced by cerebrospinal fluid. 905 40

Smooth muscle cells (SMCs) isolated from amyloid-angiopathy affected brain vessels accumulate intracellularly amyloid-beta peptide (A beta). Now we demonstrate that accumulation of A beta in SMCs can be reduced by factors secreted by macrophages - IL-1alpha, IL-6, TNF-alpha, TGF-beta1 or PGE2 - probably by stimulating the non-amyloidogenic processing of A beta precursor protein (PP). It is suggested that brain macrophages may regulate A betaPP/A beta metabolism under physiological conditions and prevent beta-amyloidosis. The disturbance of this regulatory function of brain macrophages may result in excessive production and accumulation of A beta.
 ...
PMID:Factors produced by activated macrophages reduce accumulation of Alzheimer's beta-amyloid protein in vascular smooth muscle cells. 923 43

Deposition of amyoid-beta peptide in the central nervous system is a hallmark of Alzheimer's disease and a possible cause of neurodegeneration. The factors that initiate or promote deposition of amyloid-beta peptide are not known. The transforming growth factor TGF-beta1 plays a central role in the response of the brain to injury, and increased TGF-beta1 has been found in the central nervous system of patients with Alzheimer's disease. Here we report that TGF-beta1 induces amyloid-beta deposition in cerebral blood vessels and meninges of aged transgenic mice overexpressing this cytokine from astrocytes. Co-expression of TGF-beta1 in transgenic mice overexpressing amyloid-precursor protein, which develop Alzheimer's like pathology, accelerated the deposition of amyloid-beta peptide. More TGF-beta1 messenger RNA was present in post-mortem brain tissue of Alzheimer's patients than in controls, the levels correlating strongly with amyloid-beta deposition in the damaged cerebral blood vessels of patients with cerebral amyloid angiopathy. These results indicate that overexpression of TGF-beta1 may initiate or promote amyloidogenesis in Alzheimer's disease and in experimental models and so may be a risk factor for developing Alzheimer's disease.
 ...
PMID:Amyloidogenic role of cytokine TGF-beta1 in transgenic mice and in Alzheimer's disease. 933

To clarify the immunohistochemical features of canine senile plaques (SPs) and cerebral amyloid angiopathy (CAA), the distribution of the amyloid beta protein (A beta) subtypes A beta 40 and A beta 42(43), A beta precursor protein (APP), and glial cell reaction were examined in the brains of seven aged dogs (12-18 years). A beta 42(43) was found to be deposited in all types of SPs, whereas A beta 40 was deposited only in mature (classical and primitive) plaques. CAA, which was located along parenchymal and meningeal arterioles and capillaries, consisted of both subtypes of A beta. APP was exhibited in normal and degenerative neurons and swollen neurites of mature plaques. It was, therefore, considered that A beta 42(43) in diffuse plaques might be derived from APP in neurons, while A beta 40 and A beta 42(43) in mature plaques might be generated from APP in swollen neurites in the plaque. In contrast to the case in humans, in whom deposition of A beta 40 and A beta 42(43) in the mature plaques is predominantly associated with microglial reaction, in dogs we found that it was closely associated with astroglial reaction. The present findings showed characteristics of canine SPs which are different from those of humans.
 ...
PMID:Deposition of amyloid beta protein (A beta) subtypes [A beta 40 and A beta 42(43)] in canine senile plaques and cerebral amyloid angiopathy. 934 32

Familial Danish dementia (FDD), also known as heredopathia ophthalmo-oto-encephalica, is an autosomal dominant disorder characterized by cataracts, deafness, progressive ataxia, and dementia. Neuropathological findings include severe widespread cerebral amyloid angiopathy, hippocampal plaques, and neurofibrillary tangles, similar to Alzheimer's disease. N-terminal sequence analysis of isolated leptomeningeal amyloid fibrils revealed homology to ABri, the peptide originated by a point mutation at the stop codon of gene BRI in familial British dementia. Molecular genetic analysis of the BRI gene in the Danish kindred showed a different defect, namely the presence of a 10-nt duplication (795-796insTTTAATTTGT) between codons 265 and 266, one codon before the normal stop codon 267. The decamer duplication mutation produces a frame-shift in the BRI sequence generating a larger-than-normal precursor protein, of which the amyloid subunit (designated ADan) comprises the last 34 C-terminal amino acids. This de novo-created amyloidogenic peptide, associated with a genetic defect in the Danish kindred, stresses the importance of amyloid formation as a causative factor in neurodegeneration and dementia.
 ...
PMID:A decamer duplication in the 3' region of the BRI gene originates an amyloid peptide that is associated with dementia in a Danish kindred. 1078 Oct 99

Lectin-like oxidized LDL receptor (LOX)-1 is a type II membrane protein that belongs to the C-type lectin family of molecules, which can act as a cell-surface endocytosis receptor for atherogenic oxidized LDL. LOX-1 can support binding, internalization and proteolytic degradation of oxidized LDL, but not of significant amounts of acetylated LDL, which is a well-known high-affinity ligand for class A scavenger receptors and scavenger receptor expressed by endothelial cells (SR-EC). LOX-1 is initially synthesized as a 40-kDa precursor protein with N-linked high mannose-type carbohydrate, which is further glycosylated and processed into a 50-kDa mature form. LOX-1 expression is not constitutive, but can be induced by proinflammatory stimuli, such as tumour necrosis factor-alpha, transforming growth factor-beta and bacterial endotoxin, as well as angiotensin II, oxidized LDL itself and fluid shear stress. In addition, LOX-1 expression is detectable in cultured macrophages and activated vascular smooth muscle cells. In vivo, endothelial cells that cover early atherosclerotic lesions, and intimal macrophages and smooth muscle cells in advanced atherosclerotic plaques can express LOX-1. Cell-surface LOX-1 can be cleaved through some protease activities that are associated with the plasma membrane, and released into the culture media. Purification of soluble LOX-1 and the N-terminal amino-acid sequencing identified the two cleavage sites (Arg86-Ser87 and Lys89-Ser90), both of which are located in the membrane proximal extracellular domain of LOX-1. Measurement of soluble LOX-1 in vivo may provide a novel diagnostic tool for the evaluation and prediction of atherosclerosis and vascular disease.
 ...
PMID:Roles of lectin-like oxidized LDL receptor-1 and its soluble forms in atherogenesis. 1150 27


1 2 3 4 5 Next >>