Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amyloidosis is a disease involving the fibrillar deposition of proteins in a manner that uniformly leads to the presence of green birefringence on polarization microscopy after staining the involved tissues with Congo red. In the year summarized, a wide range of new information has accumulated about this disease. In this article, attention has been paid to several newly described proteins now known to precipitate into amyloid deposits, including the proteins transthyretin, apolipoprotein A-1, cystatin C, gelsolin, amyloid beta protein, beta 2-microglobulin, scrapie protein, and islet amyloid polypeptide. The number of these amyloid-related proteins has resulted in the need for a revised nomenclature and classification scheme. The results of a recent international symposium addressing this issue are summarized in table form. The varied clinical manifestations of amyloidosis are described according to organ system, with unusual or unique areas of involvement noted. Finally, the treatment of amyloidosis and its prognosis are addressed, and new areas of possible intervention suggested.
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PMID:Amyloidosis. 204 38

Isolated amyloidomas may, albeit rarely, involve the central nervous system. There are three previous reports of amyloidomas that involved the gasserian ganglion and caused unilateral trigeminal neuropathies. The authors report the case of a 49-year-old woman with apparently isolated amyloidomas that caused slowly progressive bilateral trigeminal neuropathies. Magnetic resonance imaging of the brain revealed mild swelling of the left trigeminal nerve within the cavernous sinus and uniform enhancement with gadolinium throughout the length of the nerve. At craniotomy, the trigeminal nerve and ganglion were observed to be infiltrated by a tumor-like mass. Biopsy showed extensive infiltration of the nerve and ganglion by amyloid. Immunocytochemical studies of the amyloid were negative for immunoglobulins, kappa and lambda light chains, beta-amyloid A4 protein, transthyretin, beta 2-microglobulin, cystatin C, and gelsolin, but weak focal immunoreactivity with antiamyloid AA antibody was seen in the amyloid in vessels and in some intraneural deposits. Extensive investigations failed to reveal evidence of either systemic amyloidoses or an underlying inflammatory disorder or malignancy.
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PMID:Bilateral trigeminal amyloidoma: an unusual case of trigeminal neuropathy with a review of the literature. Case report. 793 26

Two forms of abnormal fibrillary protein deposition are considered: amyloidosis and fibrillary (immunotactoid) glomerulonephritis. Amyloid is characterised by an antiparallel, beta-pleated configuration which imparts to it a unique apple-green birefringence after Congo red staining. Inspite of its fairly constant physical properties, the chemical composition of amyloid fibrils is amazingly diverse, encomposing AA protein, light chain fragments, transthyretin, procalcitonin, islet amyloid polypeptide, atrial natriuretic peptides, beta-amyloid protein, beta-2-microglobulin, cystatin C, gelsolin, apolipoprotein A1, lyzozyme and their mutant variants. Amyloid P component and heparan sulphate proteoglycan are ubiquitous non-fibrillary amyloid components which have significant roles in the amyloidogenetic process, as do also precursor fibril proteins. Different amyloid fibril proteins relate to different amyloidosis syndromes and different histological patterns, and provide the basis for new diagnostic approaches to this disorder. Glomerular deposits in fibrillary glomerulonephritis (FGN), although often mistaken for amyloid, differ from it in its negative Congophilia, wider fibril width and highly organised, microtubular-tactoidal appearance ultrastructurally. FGN is essentially a primary glomerulopathy resulting in progressive renal failure. Despite certain differences, intriguing similarities between both entities of fibrillary deposition pose a challenge to researchers as to the mechanisms of abnormal protein crystallization and fibril formation in tissues.
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PMID:Fibrillary deposits: amyloids and tactoids. 890 98

Metabolic processing of amyloid precursor proteins is an important factor in the genesis of practically all forms of amyloidosis. Of the three major forms of systemic amyloidosis, reactive amyloid (amyloid A protein; AA) formation shows the most consistent role of partial proteolysis of serum amyloid A (SAA) to AA proteins which form fibrils. Immunoglobulin amyloidosis is also usually associated with C-terminal degradation of the fibril precursor light chain protein. Although it is commonly thought that transthyretin amyloidosis is associated with fibril formation from the tetrameric circulating plasma transthyretin, chemical analyses of transthyretin fibril deposits show significant fragmentation of the fibril protein constituents. In addition, it has been documented that proteolytic fragments are the fibril subunit proteins in gelsolin, cystatin C. Alzheimer's beta-amyloid precursor protein and apolipoprotein AI (apoAI) amyloidoses. Notable exceptions to the role of proteolysis in amyloid fibril formation would appear to be the lysozyme and beta 2-microglobulin amyloidoses. Few studies have examined the metabolism of amyloid-forming proteins. Perhaps the best data are on apoAI, which show decreased plasma residence time for the amyloidogenic Gly26Arg apoAI (1.8 d vs. normal 4.5 d). Similarly, preliminary data show increased clearance of Val30Met transthyretin when compared with the wild-type protein (18 h vs. 26 h). Also, biosynthetically 35S-labelled SAA proteins reconstituted with HDL show increased plasma clearance of murine SAA2, the amyloid fibril subunit protein, when compared with murine SAA1. Few data are available on metabolism of amyloid immunoglobulin light chain proteins, but it has been shown that radiolabelled Bence-Jones proteins are cleared very rapidly from the circulation. A better understanding of the metabolism of precursor proteins in each of the amyloid deposition diseases will give insight into the mechanisms of fibril formation and pathogenesis of amyloidosis.
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PMID:Metabolism of amyloid proteins. 891 6

Gelsolin-related amyloidosis (familial amyloidosis, Finnish type) is a rare disorder, reported worldwide in kindreds carrying a G654A or G654T gelsolin gene mutation. Facial palsy, mild peripheral neuropathy, and corneal lattice dystrophy are characteristic, but atrophic bulbar palsy, ataxia of gait, and minor cognitive impairment may occur. In histological and immunohistochemical studies of the central nervous system in 4 patients with a G654A gelsolin mutation, we found widespread spinal, cerebral, and meningeal amyloid angiopathy, with deposition of gelsolin-related amyloid (AGel). Marked extravascular deposits occurred in the dura, spinal nerve roots, and sensory ganglia. The amyloid deposits were also variably immunoreactive for apolipoprotein E (ApoE), alpha1-antichymotrypsin (alpha1-ACT), and cystatin C (Cys C). Cerebral perivascular fibrinogen immunoreactivity was occasionally noted. The patients showed posterior column degeneration and diffuse loss of myelin in the centrum semiovale with perivascular accentuation. Postmortem magnetic resonance imaging, performed on 1 patient, showed white matter lesions, colocalizing with the histological abnormalities. Our study shows that deposition of AGel in the spinal and cerebral blood vessel walls, meninges, as well as spinal nerve roots and sensory ganglia is an essential feature of this form of systemic amyloidosis and may contribute to the central nervous system symptoms.
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PMID:Gelsolin-related spinal and cerebral amyloid angiopathy. 1007 44

Cerebral amyloid angiopathy (CAA) is characterized by amyloid deposition in cortical and leptomeningeal vessels. Several cerebrovascular amyloid proteins (amyloid beta-protein (Abeta), cystatin C (ACys), prion protein (AScr), transthyretin (ATTR), gelsolin (AGel), and ABri (or A-WD)) have been identified, leading to the classification of several types of CAA. Sporadic CAA of Abeta type is commonly found in elderly individuals and patients with Alzheimer's disease. Cerebral amyloid angiopathy is an important cause of cerebrovascular disorders including lobar cerebral hemorrhage, leukoencephalopathy, and small cortical hemorrhage and infarction. We review the clinicopathological and molecular aspects of CAA and discuss the pathogenesis of CAA with future perspectives.
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PMID:Cerebral amyloid angiopathy: an overview. 1093 32

Cerebral amyloid angiopathies are defined by the presence of amyloid substance in the walls of cerebral vessels. All amyloid substances have a particular physico-chemical structure, which imparts certain specific staining properties, but the biochemical composition of different amyloid types varies. Different forms of cerebral amyloid angiopathy have been identified, based on the biochemical nature of the protein deposited (e.g. beta-amyloid, cystatin C, transthyretin, gelsolin, amyloid protein Bri, prion protein). Some cerebral amyloid angiopathies are familial; these prompted genetic studies which in turn led to a better understanding of the genes coding for different amyloid proteins. As a group, cerebral amyloid angiopathies have certain neuropathological lesions in common. Infiltration by amyloid substance results in weakening of the small vessel walls and secondary complications responsible for changes such as microinfarcts and miliary haemorrhages in the cerebral cortex, lobar haemorrhages and/or leucoencephalopathy. These changes form the basis of the neurological complications: meningeal and cerebral haemorrhages, transient ischaemic episodes, vascular dementia. However each type of hereditary cerebral amyloid angiopathy has individual clinical and histopathological features reflecting the severity of arterial involvement, the extent of amyloid deposition within or outside the central nervous system, and the association with other neurodegenarative changes.
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PMID:[Hereditary cerebral amyloid angiopathies]. 1188 14

Hereditary gelsolin amyloidosis (AGel amyloidosis) is a systemic disorder reported worldwide in kindreds with a G654A or G654T gelsolin gene mutation. The clinically characteristic peripheral nerve involvement has been poorly characterized morphologically, and its pathogenesis remains unknown. We studied peripheral nerve and skeletal muscle biopsy or autopsy specimens of 35 patients with a G654A gelsolin gene mutation. Histological, immunohistochemical, and electron microscopic studies showed consistent deposition of gelsolin amyloid (AGel), particularly in the vascular walls and perineurial sheaths. Nerve roots were more severely affected than distal nerves. The amyloid deposits also displayed variable immunoreactivity for apolipoprotein E, amyloid P component, cystatin C, and alpha-smooth muscle actin. Sural nerve morphometry showed preferential age-related large myelinated nerve fiber loss and reduction of myelin sheath cross-sectional area. There was evidence of denervation atrophy and fiber type grouping in skeletal muscle. Our study shows that marked proximal nerve involvement with AGel angiopathy is an essential feature of AGel amyloidosis. The preferential large fiber loss, not generally seen in amyloid neuropathy, may be caused by ischemia due to AGel angiopathy. Deficient actin modulation by variant gelsolin in neurons and Schwann cells, however, may alter axonal transport and myelination and contribute to AGel polyneuropathy.
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PMID:Neuromuscular pathology in hereditary gelsolin amyloidosis. 1207 40

We have undertaken a systematic proteomic approach to purify and identify secreted factors that are differentially expressed in preadipocytes versus adipocytes. Using one-dimensional gel electrophoresis combined with nanoelectrospray tandem mass spectrometry, proteins that were specifically secreted by 3T3-L1 preadipocytes or adipocytes were identified. In addition to a number of previously reported molecules that are up- or down-regulated during this differentiation process (adipsin, adipocyte complement-related protein 30 kDa, complement C3, and fibronectin), we identified four secreted molecules that have not been shown previously to be expressed differentially during the process of adipogenesis. Pigment epithelium-derived factor, a soluble molecule with potent antiangiogenic properties, was found to be highly secreted by preadipocytes but not adipocytes. Conversely, we found hippocampal cholinergic neurostimulating peptide, neutrophil gelatinase-associated lipocalin, and haptoglobin to be expressed highly by mature adipocytes. We also used liquid chromatography-based separation followed by automated tandem mass spectrometry to identify proteins secreted by mature adipocytes. Several additional secreted proteins including resistin, secreted acidic cysteine-rich glycoprotein/osteonectin, stromal cell-derived factor-1, cystatin C, gelsolin, and matrix metalloprotease-2 were identified by this method. To our knowledge, this is the first study to identify several novel secreted proteins by adipocytes by a proteomic approach using mass spectrometry.
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PMID:A proteomic approach for identification of secreted proteins during the differentiation of 3T3-L1 preadipocytes to adipocytes. 1209 21

Cerebral amyloid angiopathy (CAA) is the term used to describe deposition of amyloid in the walls of arteries, arterioles and, less often, capillaries and veins of the central nervous system. CAAs are an important cause of cerebral hemorrhage and may also result in ischemic lesions and dementia. A number of amyloid proteins are known to cause CAA. The most common sporadic CAA, caused by A beta deposition, is associated with aging and is a common feature of Alzheimer disease (AD). CAA occurs in several familial conditions, including hereditary cerebral hemorrhage with amyloidosis of Icelandic type caused by deposition of mutant cystatin C, hereditary cerebral hemorrhage with amyloidosis Dutch type and familial AD with deposition of either A beta variants or wild-type A beta, the transthyretin-related meningo-vascular amyloidoses, gelsolin as well as familial prion disease-related CAAs and the recently described BRI2 gene-related CAAs in familial British dementia and familial Danish dementia. This review focuses on the morphological, biochemical, and genetic aspects as well as the clinical significance of CAAs with special emphasis on the BRI2 gene-related cerebrovascular amyloidoses. We also discuss data relevant to the pathomechanism of the different forms of CAA with an emphasis on the most common A beta-related types.
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PMID:Sporadic and familial cerebral amyloid angiopathies. 1214 3


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