Abstract：
:Massive production and accumulation of a single abnormal protein may constitute a major toxic burden for the cell and even compromise the organism's long-term viability. Consequently, adaptation and survival have forced evolution to create 'quality control' mechanisms that detect, monitor, and often degrade such abnormally folded gene products, in which molecular chaperones are key players. Notwithstanding this, there are numerous examples of misfolded proteins which, in spite of being recognized as aberrant and efficiently discarded by cellular quality control, still retain some of the functional properties of their wild-type counterparts, so that their maintenance in the cell would be beneficial for the organism. Herein are described the cellular roles of molecular chaperones and some new insights on the mechanisms by which they influence the development of human diseases caused by mutations that lead to protein misfolding. A special emphasis is given to cystic fibrosis, a classical genetic disorder resulting from the retention and degradation of a mutant, albeit functional, protein by the endoplasmic reticulum quality control. This particular system has been a good example to describe the mechanisms that are likely to be shared by a number of protein substrates, to define the common characteristics of the mutants, as well as to identify the mechanistic intervenients in their retention and degradation. Finally, new approaches aimed at correcting protein folding defects are discussed, including the potential of molecular chaperones (e.g., through RNA interference) as novel therapeutic targets, and the usage of chemical or pharmacological chaperones as new therapeutic agents.
journal_name
J Inherit Metab Disjournal_title
Journal of inherited metabolic diseaseauthors
Amaral MDdoi
10.1007/s10545-006-0251-xsubject
Has Abstractpub_date
2006-04-01 00:00:00pages
477-87issue
2-3eissn
0141-8955issn
1573-2665journal_volume
29pub_type
杂志文章,评审abstract：:Glycogen storage disease type Ib (GSD-Ib) is caused by a deficiency in the ubiquitously expressed glucose-6-phosphate (G6P) transporter (G6PT or SLC37A4). The primary function of G6PT is to translocate G6P from the cytoplasm into the lumen of the endoplasmic reticulum (ER). Inside the ER, G6P is hydrolyzed to glucose ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/s10545-018-0180-5
更新日期：2018-11-01 00:00:00
abstract：:The glycine uptake in cultured fibroblasts was studied in three children with non-ketotic hyperglycinaemia, one child with D-glyceric acidaemia and hyperglycinaemia and in six normal children, using an improved assay system giving individual protein correction. It was shown that all hyperglycinaemic children had norma...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF02338974
更新日期：1983-01-01 00:00:00
abstract：:Our series of studies on Hunter disease in Japanese patients showed allelic heterogeneity of IDS gene mutations, genotype/phenotype correlation and racial differences in distribution of mutations. Twenty-five different small mutations have been characterized. Small mutations in the Japanese population are widely distr...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1005363414792
更新日期：1998-02-01 00:00:00
abstract：:Animal models of inborn errors of metabolism are useful for investigating the pathogenesis associated with the corresponding human disease. Since the mechanisms involved in the pathophysiology of succinate semialdehyde dehydrogenase (SSADH) deficiency (Aldh5a1; OMIM 271980) are still not established, in the present st...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-007-0599-6
更新日期：2007-10-01 00:00:00
abstract：:Wilson disease (WD) is an autosomal recessive disorder of copper accumulation leading to liver and/or brain damage. In this paper, we describe the results of a pilot study of screening for WD using ceruloplasmin determinations in dried blood samples. Specimens were collected from children aged 1 to 6 years who were se...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1005455401076
更新日期：1999-02-01 00:00:00
abstract：:Danon disease is an X-linked disorder resulting from mutations in the lysosome-associated membrane protein-2 (LAMP2) gene. We report a male patient with skeletal myopathy, mental retardation, and massive hypertrophic obstructive cardiomyopathy necessitating heart transplantation. Immunohistochemistry of skeletal muscl...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-009-1097-9
更新日期：2009-12-01 00:00:00
abstract：:Krabbe's disease was diagnosed prenatally using cultured amniotic fluid cells and the diagnosis confirmed using fetal brain, liver and cultured fetal skin fibroblasts. The enzyme defect was demonstrated by assay of galactocerebrosidase and lactocerebrosidase I, and by hydrolysis of the chromogenic analogue, 2-hexadeca...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01805686
更新日期：1978-01-01 00:00:00
abstract：:The activity (mean +/- SD) of galactose-1-phosphate uridyl transferase in two long-term lymphoid cell lines from Caucasian patients with transferase deficiency galactosaemia, a heterozygote, and eight normal subjects was 0, 78 and 168 +/- 55 nmol UDPG consumed (mg protein)-1h-1, respectively. Also, no activity was fou...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01799977
更新日期：1987-01-01 00:00:00
abstract：:Mucopolysaccharidosis type III (MPS III) or Sanfilippo disease is an orphan inherited lysosomal storage disease and one of the most common MPS subtypes. The classical presentation is an infantile-onset neurodegenerative disease characterised by intellectual regression, behavioural and sleep disturbances, loss of ambul...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1002/jimd.12316
更新日期：2021-01-01 00:00:00
abstract：:Glutaric aciduria type I is an inborn error of organic acid metabolism that demonstrates a particular temporal vulnerability (acute encephalopathic episodes in infancy) and a spatial vulnerability (acute striatal necrosis, focused on the putamen). Excitotoxic mechanisms involving 3-hydroxyglutaric acid as the major ne...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1023/B:BOLI.0000045767.42193.97
更新日期：2004-01-01 00:00:00
abstract：:Genetic disorders of purine and pyrimidine (PP) metabolism are under-reported and infrequently mentioned in the general literature, as well as in reviews dedicated to other inborn errors of metabolism. Owing to limited awareness, relatively recent recognition, as well as considerable phenotypic variation, these disord...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/s10545-009-1094-z
更新日期：2009-04-01 00:00:00
abstract：:Recently, we reported that baicalein 5,6,7-trimethyl ether (BTM), a flavonoid, is capable of activating fatty acid beta-oxidation in X-linked adrenoleukodystrophy (X-ALD) fibroblasts (FEBS Lett. 2005; 579: 409-414). The objective of this study was to clarify whether BTM activates peroxisomal and/or mitochondrial fatty...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-008-0857-2
更新日期：2008-06-01 00:00:00
abstract：:Creatine transporter deficiency was discovered in 2001 as an X-linked cause of intellectual disability characterized by cerebral creatine deficiency. This review describes the current knowledge regarding creatine metabolism, the creatine transporter and the clinical aspects of creatine transporter deficiency. The cond...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/s10545-014-9713-8
更新日期：2014-09-01 00:00:00
abstract：:Diagnostic information is supplied for the early detection of subacute and chronic forms of type I tyrosinaemia. ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01799947
更新日期：1991-01-01 00:00:00
abstract：:Four neonates with a positive phenylalanine screening test (Phe concentrations between 258 and 1250 micromol/L) were investigated further to differentiate between phenylalanine hydroxylase (PAH) deficiency and variant hyperphenylalaninaemia (HPA) forms. In patients 1 and 2 a tetrahydrobiopterin (BH4) load caused a sig...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1010596317296
更新日期：2001-06-01 00:00:00
abstract：OBJECTIVE:To analyse diagnostic value of somato-sensory evoked potentials (SEP), magnetic resonance imaging (MRI), and clinical neurological examination in the decision for decompression surgery in mucopolysaccharidosis (MPS) VI patients with craniocervical cord compression (CCJ). METHODS:We retrospectively analysed n...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-013-9591-5
更新日期：2013-11-01 00:00:00
abstract：:S-Adenosylhomocysteine (S-AdoHcy) hydrolase activity in a lymphoblastoid cell line from a patient with adenosine deaminase deficiency disease (ADA(-)LCL) was found to be approximately 60% of that in ADA (+)lymphoblastoid cell lines. S-AdoHcy hydrolase of ADA(-)LCL was more sensitive to inhibition by 2'-deoxyadenosine ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF02263651
更新日期：1981-01-01 00:00:00
abstract：:Hypoglycaemia induced by fructose administration is one of the diagnostic clues to fructose-1,6-diphosphatase (FDPase) deficiency (McKusick 229700). However, the pathological mechanism of this reactive hypoglycaemia is not fully known. This paper describes two siblings with FDPase deficiency, diagnosed enzymatically i...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01800012
更新日期：1992-01-01 00:00:00
abstract：:We report D-2-hydroxyglutaric aciduria in a neonate with intracranial haemorrhage and absence of the corpus callosum. D-2-hydroxyglutaric acid was confirmed by specific chiral derivatization gas chromatography-mass spectrometry. Absence of the corpus callosum and spontaneous neonatal intracranial haemorrhage should ra...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1024000202364
更新日期：2003-01-01 00:00:00
abstract：:We report two novel mutations in two Japanese patients with glycogen storage disease type IIIa (GSD IIIa). In addition, we review the literature on mutations in GSD III to understand better the molecular basis of GSD III. In our first case, the homozygous A-to-C mutation at the acceptor site of intron 5 (IVS5-2A > C) ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1005695229464
更新日期：2000-03-01 00:00:00
abstract：:Cholesterol is known to be a significant constituent of the central nervous system. It also plays an important role in developmental pathways to form the human brain, such as the Sonic Hedgehog pathway. Disturbances in the formation of cholesterol may therefore be expected to cause brain malformations and brain dysfun...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,评审
doi：10.1007/s10545-005-7055-2
更新日期：2005-01-01 00:00:00
abstract：:Urea and creatinine were measured by Kodak Ektachem methods and methylmalonic acid by stable-isotope gas chromatography-mass spectrometry in 24 urine samples from patients with methylmalonic acidaemia. For each sample analyses were performed both directly on the liquid urine and on an aliquot which had been blotted on...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01799839
更新日期：1996-01-01 00:00:00
abstract：:Twenty-one patients have been diagnosed with glutaric aciduria type I over a 16-year period in the Republic of Ireland, 11 following clinical presentation and 10 following a high-risk screen. Nineteen have been managed with diet. Eight patients have died, of whom 7 were diagnosed clinically. Six had dystonic and one s...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/B:BOLI.0000045777.82784.74
更新日期：2004-01-01 00:00:00
abstract：:The retinal and neurological complications of abetalipoproteinaemia may be preventable by replacing vitamins A and E from an early age, but their role in adult presentations is less clear. Two adult females with abetalipoproteinaemia have received 8 and 10 years respectively of replacement therapy with vitamins A, E a...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01799870
更新日期：1988-01-01 00:00:00
abstract：:Retinitis pigmentosa can occur as a complication of mevalonate kinase deficiency. This may be due to the unique isoprenoid metabolism in the retina. Early detection requires awareness on the part of the treating physician. ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-005-0178-7
更新日期：2005-01-01 00:00:00
abstract：:Investigations into the biochemical markers associated with executive function (EF) impairment in children with early and continuously treated phenylketonuria (ECT-PKU) remain largely phenylalanine-only focused, despite experimental data showing that a high phenylalanine:tyrosine (phe:tyr) ratio is more strongly assoc...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,多中心研究
doi：10.1007/s10545-010-9211-6
更新日期：2010-12-01 00:00:00
abstract：:A female patient with isovaleric acidaemia had a successful outcome from pregnancy. ...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1023/a:1022837416232
更新日期：2002-12-01 00:00:00
abstract：BACKGROUND:Life expectancy of patients with glycogen storage disease (GSD) type I has improved considerably, opening new problems correlated with adult age. In females polycystic ovaries (PCOs) has been described as frequently associated with the disease, however successful pregnancies have been reported. Whether or no...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章,多中心研究
doi：10.1007/s10545-012-9490-1
更新日期：2013-01-01 00:00:00
abstract：BACKGROUND:Morphology and function of Fabry cardiomyopathy has been previously studied by echocardiography and cardiac magnetic resonance (CMR). However, the value of electrocardiography (ECG) in relation to these two techniques remains largely unknown. METHODS:One hundred fifty genetically confirmed Fabry patients we...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/s10545-012-9540-8
更新日期：2013-09-01 00:00:00
abstract：:Phosphatidylethanolamine plasmalogen levels were determined in erythrocytes from controls and 13 patients with the cerebro-hepato-renal (Zellweger) syndrome. It was found that in Zellweger patients 20 weeks of age or younger, erythrocyte phosphatidylethanolamine plasmalogen levels were lowered whereas in older patient...
journal_title：Journal of inherited metabolic disease
pub_type： 杂志文章
doi：10.1007/BF01800482
更新日期：1986-01-01 00:00:00
