Abstract：
:Over the past several years, considerable progress has been made in the development of gene therapy as a therapeutic strategy for a variety of inherited metabolic diseases, including neuropathic lysosomal storage disorders (LSDs). The premise of gene therapy for this group of diseases is borne of findings that genetic modification of a subset of cells can provide a more global benefit by virtue of the ability of the secreted lysosomal enzymes to effect cross-correction of adjacent and distal cells. Preclinical studies in small and large animal models of these disorders support the application of either a direct in vivo approach using recombinant adeno-associated viral vectors or an ex vivo strategy using lentiviral vector-modified hematopoietic stem cells to correct the neurological component of these diseases. Early clinical studies utilizing both approaches have begun or are in late-stage planning for a small number of neuropathic LSDs. Although initial indications from these studies are encouraging, it is evident that second-generation vectors that exhibit a greater safety profile and transduction activity may be required before this optimism can be fully realized. Here, I review recent progress and the remaining challenges to treat the neurological aspects of various LSDs using this therapeutic paradigm.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Cheng SHdoi
10.1194/jlr.R047175subject
Has Abstractpub_date
2014-09-01 00:00:00pages
1827-38issue
9eissn
0022-2275issn
1539-7262pii
jlr.R047175journal_volume
55pub_type
杂志文章,评审abstract：:Ethanolamine phosphotransferase (EPT)1, also known as selenoprotein 1 (SELENOI), is an enzyme that transfers phosphoethanolamine from cytidine diphosphate-ethanolamine to lipid acceptors to produce ethanolamine glycerophospholipids, such as diacyl-linked phosphatidylethanolamine (PE) and ether-linked plasmalogen [1-al...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P081620
更新日期：2018-06-01 00:00:00
abstract：:Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that regulates hepatic low-density lipoprotein receptor (LDLR) levels in humans. PCSK9 has also been shown to regulate the levels of additional membrane-bound proteins in vitro, including the very low-density lipoprotein receptor (VLDLR), apol...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M006635
更新日期：2010-09-01 00:00:00
abstract：:Alcoholic liver disease (ALD) is the most prevalent type of chronic liver disease with significant morbidity and mortality worldwide. ALD begins with simple hepatic steatosis and progresses to alcoholic steatohepatitis, fibrosis, and cirrhosis. The severity of hepatic steatosis is highly associated with the developmen...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R119000547
更新日期：2020-04-01 00:00:00
abstract：:Sphingolipids (SLs) have been implicated in numerous important cellular biologies; however, their study has been hindered by the complexities of SL metabolism. Furthermore, enzymes of SL metabolism represent a dynamic and interconnected network in which one metabolite can be transformed into other bioactive SLs throug...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M089714
更新日期：2019-04-01 00:00:00
abstract：:High density lipophorin (HDLp is the main lipoprotein found in resting insect hemolymph. It has, in general, two molecules of apolipoproteins: apoLp-I (250 kDa) and apoLp-II (80 kDa) and a variable lipid content which ranges from 35% to 59% (w/w). Diacylglycerols (DG), phospholipids (PL), and hydrocarbons (HC) are the...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-03-01 00:00:00
abstract：:The central region of apolipoprotein A-I (apoA-I), spanning residues 143--165, has been implicated in lecithin:cholesterol acyltransferase (LCAT) activation and also in high density lipoprotein (HDL) structural rearrangements. To examine the role of individual amino acids in these functions, we constructed, overexpres...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2001-03-01 00:00:00
abstract：:Lipoprotein (a) [Lp(a)] is a highly atherogenic lipid particle. Although earlier reports suggested that Lp(a) levels are mostly determined by genetic factors, several recent studies have revealed that Lp(a) induction is also caused by chronic inflammation. Therefore, we aimed to examine whether cytokine blockade by mo...
journal_title：Journal of lipid research
pub_type： 临床试验,杂志文章
doi：10.1194/jlr.P052209
更新日期：2015-05-01 00:00:00
abstract：:The accurate quantitation of high density lipoproteins has recently assumed greater importance in view of studies suggesting their negative correlation with coronary heart disease. High density lipoproteins may be estimated by measuring cholesterol in the plasma fraction of d > 1.063 g/ml. A more practical approach is...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1978-01-01 00:00:00
abstract：:An online, two-dimensional (2D) liquid chromatography (LC) quadrupole time-of-flight mass spectrometry (QToF-MS) method was developed for lipid profiling of rat peritoneal surface layers, in which the lipid classes and species could be simultaneously separated in one injection with a significantly increased sensitivit...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D007567
更新日期：2010-09-01 00:00:00
abstract：:A new sample preparation method coupled to GC-MS analysis was developed and validated for quantification of sulfate esters of pregnenolone (PREG-S) and dehydroepiandrosterone (DHEA-S) in rat brain. Using a solid-phase extraction recycling protocol, the results show that little or no PREG-S and DHEA-S (<1 pmol/g) is pr...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400244-JLR200
更新日期：2004-12-01 00:00:00
abstract：:Biliary cholesterol secretion is ordinarily tightly coupled to phosphatidylcholine (PC) secretion. Bile PCs are distinct in composition and predominantly composed of molecular species with 16:0 in the sn-1 position and 18:2 and 18:1 in the sn-2 position. In an attempt to acutely change the composition of biliary PCs a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-06-01 00:00:00
abstract：:Apolipoprotein C-II (apoC-II) plays a critical role in the metabolism of plasma lipoproteins as an activator for lipoprotein lipase. Human apoC-II consists of 79 amino acid residues (pro-apoC-II). A minor fraction is converted to a mature form by cleavage at the site QQDE releasing the 6 amino-terminal residues. We ha...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-11-01 00:00:00
abstract：:Acyl-CoA:monoglyceride acyltransferase in microsomal preparations from the small intestine of the rat has been measured by means of continuous recording spectrophotometry. The reaction of 5,5'-dithiobis(2-nitrobenzoic acid) with CoA has been employed for this assay and optimal conditions for the reaction have been def...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1969-07-01 00:00:00
abstract：:Conjugated linoleic acid (CLA), a mixture of isomers of linoleic acid, has previously been shown to be able to decrease porcine subcutaneous (SC) adipose tissue levels while increasing the count of intramuscular (IM) adipose tissue in vivo. However, the underlying mechanisms through which it acts are poorly understood...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600525-JLR200
更新日期：2007-08-01 00:00:00
abstract：:Inflammation has been proposed to impair HDL function and reverse cholesterol transport (RCT). We investigated the effects of inflammation mediated by zymosan, a yeast glucan, on multiple steps along the RCT pathway in vivo and ex vivo. Acute inflammation with 70 mg/kg zymosan impaired RCT to plasma, liver, and feces ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M011122
更新日期：2011-05-01 00:00:00
abstract：:Characterization of the chemical form and stereo-specificity of the fatty acid derivatives of arachidonic and linoleic acid in psoriatic epidermis is needed to define the enzymatic origin of these compounds and their possible role in pathogenesis. In an analysis of psoriatic skin scales, both free and esterified 13-hy...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1990-01-01 00:00:00
abstract：:In studies of cebus monkey plasma lipoproteins, we have used an ultracentrifugally generated density gradient to isolate two distinct species of low density lipoproteins (LDL). Compositional analyses revealed that each of the ultracentrifugally isolated fractions was enriched in cholesteryl esters and contained a sing...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1989-05-01 00:00:00
abstract：:Dietary lipids are taken up as FAs by the intestinal epithelium and converted by diacylglycerol acyltransferase (DGAT) enzymes into triglycerides, which are packaged in chylomicrons or stored in cytoplasmic lipid droplets (LDs). DGAT1-deficient patients suffer from vomiting, diarrhea, and protein losing enteropathy, i...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M094201
更新日期：2019-10-01 00:00:00
abstract：:3 alpha,7 alpha-dihydroxy-5 beta-cholestan-26-oic acid (DHCA) and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan-26-oic acid (THCA) are metabolized into chenodeoxycholic acid and cholic acid, respectively, through oxidation and cleavage of the terminal three carbons of the side chain. The present study was desig...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1980-02-01 00:00:00
abstract：:The fusogenic properties of sulfatide-containing 1,2-dioleoyl-3-sn -phosphatidylethanolamine (DOPE) small unilamellar vesicles (SUVs) in the presence of CaCl2 were studied by mixing membrane lipids based on an assay of fluorescence resonance energy transfer (FRET). Fusion of the vesicles was also confirmed by mixing a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1999-07-01 00:00:00
abstract：:We have investigated the extent to which modifications in the essential fatty acid content of mammalian cells can affect prostaglandin production. Swiss mouse 3T3 cells stimulated with the calcium ionophore A23187 produced 1.7 to 7 times more prostaglandin E(2) (PGE(2)) when the cultures were supplemented with linolei...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1982-05-01 00:00:00
abstract：:Remnant-like emulsions were prepared with lipid compositions similar to remnants derived from triacylglycerol-rich lipoproteins. When injected into the bloodstream of conscious mice the remnant-like emulsions labeled with cholesteryl[13C]oleate were metabolized in the liver and the appearance of 13CO2 in the breath wa...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1998-03-01 00:00:00
abstract：:Previous studies have shown that reduced levels of the adipocyte fatty acid binding protein (FABP)4 (AFABP/aP2), result in metabolic improvement including potentiated insulin sensitivity and attenuated atherosclerosis. Mechanistically, pharmacologic or genetic inhibition of FABP4 in macrophages upregulates UCP2, atten...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M074542
更新日期：2017-07-01 00:00:00
abstract：:Fluorescence energy transfer from dehydroergosterol (DHE) to dansylated lecithin (DL) was used to characterize lecithin-cholesterol vesicles in the presence of the bile salt, sodium taurocholate. At lipid concentrations approximating physiological levels, exposure of fluorescently labeled vesicles to the bile salt led...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2001-06-01 00:00:00
abstract：:Serum triglyceride (TG) levels are increased in extremely obese individuals, indicating abnormalities in lipid metabolism and insulin resistance. We carried out a genome scan for serum TG in 320 nuclear families segregating extreme obesity and normal weight. Three hundred eighty-two Marshfield microsatellite markers (...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M400391-JLR200
更新日期：2005-03-01 00:00:00
abstract：:Trihydroxyoctadecenoic acids (TriHOMEs) are linoleic acid-derived oxylipins with potential physiological relevance in inflammatory processes as well as in maintaining an intact skin barrier. Due to the high number of possible TriHOME isomers with only subtle differences in their physicochemical properties, the stereoc...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D087429
更新日期：2018-10-01 00:00:00
abstract：:Apolipoprotein L is a newly recognized component of human plasma lipoproteins. Mainly associated with apoA-I-containing lipoproteins, it is a marker of distinct HDL subpopulations. In an effort to gain inference as to its as yet unknown function, we studied biological determinants of apoL levels in human plasma. The d...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2000-08-01 00:00:00
abstract：:Reduced white adipose tissue (WAT) LPL activity delays plasma clearance of TG-rich lipoproteins (TRLs). We reported the secretion of apoC-I, an LPL inhibitor, from WAT ex vivo in women. Therefore we hypothesized that WAT-secreted apoC-I associates with reduced WAT LPL activity and TRL clearance. WAT apoC-I secretion a...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P064170
更新日期：2016-06-01 00:00:00
abstract：:This study was undertaken to develop techniques for measuring absolute rates of sterol synthesis in extrahepatic tissues in vitro and to estimate the magnitude of the errors inherent in the use of various 14C-labeled substrates for such measurements. Initial studies showed that significant errors were introduced when ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1979-08-01 00:00:00
abstract：:When stimulated, rat serosal mast cells degranulate and secrete a cytoplasmic neutral protease, chymase. We studied the fragmentation of apolipoprotein (apo) A-I during proteolysis of HDL(3) by chymase, and examined how chymase-dependent proteolysis interfered with the binding of eight murine monoclonal antibodies (Ma...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：2000-06-01 00:00:00
