Search results for "amyloidosis"
showing 10 items of 79 documents
A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model
2004
Alzheimer disease (AD) is characterized by excessive deposition of amyloid beta-peptides (A beta peptides) in the brain. In the nonamyloidogenic pathway, the amyloid precursor protein (APP) is cleaved by the alpha-secretase within the A beta peptide sequence. Proteinases of the ADAM family (adisintegrin and metalloproteinase) are the main candidates as physiologically relevant alpha-secretases, but early lethality of knockout animals prevented a detailed analysis in neuronal cells. To overcome this restriction, we have generated transgenic mice that overexpress either ADAM10 or a catalytically inactive ADAM10 mutant. In this report we show that a moderate neuronal overexpression of ADAM10 i…
Indication of a common origin of German and American Families with Familial Amyloidneuropathy Typ II
1999
Abstract The classification of familial amyloid neuropathies (FAP) is traditionally based on clinical and regional aspects. In the last 10 years more than 40 mutations of the transthyretin gene have been found to be responsible for different clinical forms of amyloidosis including familial FAP.FAP II is caused by a mutation on the codon 58 of the transthyretin gene. Only two american kindreds (the Maryland/German and the Ohio family) have previously been reported with FAP II starting in the 3rd or 4th decade by sensory disturbances of the hands typically as a carpal tunnel syndrome. We report on a german family with FAP II from the rhine river area south of Mainz. Four members with typical …
Therapy of ATTR Cardiac Amyloidosis: Current Indications
2023
Transthyretin cardiac amyloidosis is a restrictive cardiomyopathy caused by extracellular deposition in the heart of amyloid fibrils derived from plasma transthyretin (ATTR), either in its hereditary (ATTRh) or acquired (ATTRwt) forms. Cardiac amyloidosis has a very poor prognosis if therapy is not started promptly. Therefore, it is very important to recognize cardiac amyloidosis early in order to immediately start a treatment capable of modifying the prognosis. Treatment of cardiac amyloidosis is not easy, often requiring a multidisciplinary team. New RNA-interfering drugs (such as patisiran) have been devised and are effective in the treatment of ATTRh amyloidosis. Tafamidis (a stabilizer…
Parenteral nutrition improves nutritional status, autonomic symptoms and QoL in patients with TTR-FAP
2015
Background Transthyretin related familial amyloidotic polyneuropathy (TTR-FAP) is an inherited form of amyloidosis, leading to death in about 10 years in most cases for cardiac failure or wasting syndrome. Previous study showed that modified body mass index (mBMI) was related to time before death, duration of gastrointestinal disturbances, malabsorption and functional capacity. Futhermore, outcome after liver tranplantation was greater in patients with an mBMI over 600.
Amyloid P component--a special type of collagen?
1978
The localization of amyloid P-components is demonstrated by immunofluorescence microscopy in normal human tissue (kidney, spleen, liver). The relation to collagen and to amyloidosis is discussed.
α-Synuclein expression levels do not significantly affect proteasome function and expression in mice and stably transfected PC12 cell lines
2004
α-Synuclein (α-syn) is a small protein of unknown function that is found aggregated in Lewy bodies, the histopathological hallmark of sporadic Parkinson disease and other synucleinopathies. Mutations in the α-syn gene and a triplication of its gene locus have been identified in early onset familial Parkinson disease. α-Syn turnover can be mediated by the proteasome pathway. A survey of published data may lead to the suggestion that overexpression of α-syn wild type, and/or their variants (A53T and A30P), may produce a decrease in proteasome activity and function, contributing to α-syn aggregation. To investigate the relationship between synuclein expression and proteasome function we have s…
Human apolipoprotein A-I natural variants: molecular mechanisms underlying amyloidogenic propensity
2012
Human apolipoprotein A-I (apoA-I)-derived amyloidosis can present with either wild-type (Wt) protein deposits in atherosclerotic plaques or as a hereditary form in which apoA-I variants deposit causing multiple organ failure. More than 15 single amino acid replacement amyloidogenic apoA-I variants have been described, but the molecular mechanisms involved in amyloid-associated pathology remain largely unknown. Here, we have investigated by fluorescence and biochemical approaches the stabilities and propensities to aggregate of two disease-associated apoA-I variants, apoA-IGly26Arg, associated with polyneuropathy and kidney dysfunction, and apoA-ILys107-0, implicated in amyloidosis in severe…
Crosstalk between angiotensin and the nonamyloidogenic pathway of Alzheimer's amyloid precursor protein.
2017
The association between hypertension and an increased risk for Alzheimer's disease (AD) and dementia is well established. Many data suggest that modulation of the renin-angiotensin system may be meaningful for the prevention and therapy of neurodegenerative disorders, in particular AD. Proteolytic cleavage of the amyloid precursor protein (APP) by α-secretase precludes formation of neurotoxic Aβ peptides and is expected to counteract the development of AD. An established approach for the up-regulation of α-secretase cleavage is the activation of G protein-coupled receptors (GPCRs). Therefore, our study aimed to analyze whether stimulation of angiotensin AT1 or AT2 receptors stably expressed…
Clinical symptomatic de novo systemic transthyretin amyloidosis 9 years after domino liver transplantation
2009
Four years ago, Stangou et al. reported a patient who developed clinical symptoms of amyloidosis 8 years after domino liver transplantation (DLT). In order to alleviate the graft shortage, livers from patients with familial amyloidotic polyneuropathy (FAP) are used as domino grafts for other patients under the assumption that several decades will pass before clinical symptoms due to amyloid accumulation emerge. We now report on another case, the third reported case in the literature, of de novo systemic amyloidosis in a 75-year-old woman 9 years after DLT. The patient underwent DLT at 65 years of age for hepatocellular carcinoma exceeding the Milan criteria in hepatitis C cirrhosis. Transar…
The Influence of Insulin on Local Amyloidosis of the Islets of Langerhans and Insulinoma
1980
Summary Amyloid-containing islets of Langerhans from the pancreas of 75 diabetics and one case of an amyloid-containing insulinoma were investigated. By light and electron microscopy, amyloid deposits were observed between the B cells and adjacent capillaries. The cytoplasm of B cells and extracellular amyloid display immunohistological binding of anti-insulin antibody. Correspondingly, ferritin-labeled anti-insulin antibody was found by electron microscopy on and between the amyloid fibrils. Insulin or proinsulin (or a protein closely related to insulin) thus appears to be a.component of the protein which constitutes the amyloid. The molecular weight and mode of deposition of this form of …