Abstract：
:Developing cellular models of sporadic Alzheimer's disease (sAD) is challenging due to the unknown initiator of disease onset and the slow disease progression that takes many years to develop in vivo. The use of human induced pluripotent stem cells (iPSCs) has revolutionised the opportunities to model AD pathology, investigate disease mechanisms and screen potential drugs. The majority of this work has, however, used cells derived from patients with familial AD (fAD) where specific genetic mutations drive disease onset. While these provide excellent models to investigate the downstream pathways involved in neuronal toxicity and ultimately neuronal death that leads to AD, they provide little insight into the causes and mechanisms driving the development of sAD. In this review we compare the data obtained from fAD and sAD iPSC-derived cell lines, identify the inconsistencies that exist in sAD models and highlight the potential role of Aβ clearance mechanisms, a relatively under-investigated area in iPSC-derived models, in the study of AD. We discuss the development of more physiologically relevant models using co-culture and three-dimensional culture of iPSC-derived neurons with glial cells. Finally, we evaluate whether we can develop better, more consistent models for sAD research using genetic stratification of iPSCs and identification of genetic and environmental risk factors that could be used to initiate disease onset for modelling sAD. These considerations provide exciting opportunities to develop more relevant iPSC models of sAD which can help drive our understanding of disease mechanisms and identify new therapeutic targets.
journal_name
Neurochem Resjournal_title
Neurochemical researchauthors
Rowland HA,Hooper NM,Kellett KABdoi
10.1007/s11064-018-2663-zsubject
Has Abstractpub_date
2018-12-01 00:00:00pages
2179-2198issue
12eissn
0364-3190issn
1573-6903pii
10.1007/s11064-018-2663-zjournal_volume
43pub_type
杂志文章,评审abstract：:The concentration of vitamin E (alpha-tocopherol) was measured in samples of cortex from patients with Alzheimer's disease (AD), fetuses with Down's syndrome (DS), and also in a group of centenarians. The mean tocopherol concentrations in the two patient groups did not differ significantly from appropriate controls. W...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00965511
更新日期：1989-12-01 00:00:00
abstract：:The release of preloaded D-[3H]aspartate, an unmetabolizable analogue of L-glutamate, was studied in superfused hippocampal slices from 7-day-old and 3-month-old (adult) mice under various cell-damaging conditions, including hypoxia, hypoglycemia, ischemia, oxidative stress and the presence of free radicals and metabo...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1023/a:1021052725921
更新日期：1999-08-01 00:00:00
abstract：:Experimental studies demonstrate that inhaled anesthetics can cause neurodegeneration and neurobehavioral dysfunctions. Evidence suggests changes in cerebral metabolism following inhaled anesthetics treatment can perturb cerebral homeostasis, which may be associated with their induced neurotoxicity. Seven-day-old rat ...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-015-1529-x
更新日期：2015-04-01 00:00:00
abstract：:The effects of vinpocetine on internal Na+ (Na(i)), cAMP accumulation, internal Ca2+ (Ca(i)) and excitatory amino acid neurotransmitters release, under resting and under depolarized conditions, was investigated in rat striatum synaptosomes. Veratridine (20 microM) or high K+ (30 mM) were used as depolarizing agents. R...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1023/a:1021164418478
更新日期：1999-12-01 00:00:00
abstract：:We evaluated oxidative stress associated with a model of experimental epilepsy. Male Wistar rats were injected i.p. with 150 mg/kg convulsant 3-mercaptopropionic acid and decapitated in two stages: during seizures or in the post-seizure period. Spontaneous chemiluminescence, levels of thiobarbituric acid reactive subs...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF03177490
更新日期：1998-12-01 00:00:00
abstract：:An analytical method for the determination of saturated very long chain (VLC) fatty acids in the serum has been devised. Free fatty acids obtained after hydrolysis of total lipid extracts were converted into p-bromophenacyl esters. The derivatives were purified in two sequential steps by clean-up on C18 reversed-phase...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00968082
更新日期：1984-12-01 00:00:00
abstract：:Subacute exposure to manganese (Mn) produced Parkinson's disease-like syndrome called Manganism. Chronic onset and progression are characteristics of Manganism, therefore, this study aimed to examine Mn toxicity following chronic exposures. Male Sprague-Dawley rats were injected Mn2+ 1 and 5 mg/kg, every 10 days for 1...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-020-03059-2
更新日期：2020-08-01 00:00:00
abstract：:Oxidation of [2,3-14C]succinate in the intramitochondrial Krebs cycle was used as a probe to investigate the effect of ammonia on protein incorporation and Krebs cycle oxidation of succinate carbons in isolated rat hepatocytes. At low concentrations of ammonium chloride (0.1 to 0.5 mM) a slight increase in 14CO2 forma...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00965690
更新日期：1991-07-01 00:00:00
abstract：:The uptake of radioactive ethanolamine has been studied in exclusively neuronal and glial cell cultures from dissociated cerebral hemispheres of chick embryos. Both cell types show saturable kinetics; neurons have an apparent Km of 6.7 microM, Vmax 41.4 pmol mg prot.-1 min-1 and glial cells a Km of 119.6 microM, Vmax ...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00965162
更新日期：1986-01-01 00:00:00
abstract：:The effects of neuroleptic treatments on dopamine transporters and on dopamine receptors was investigated in the forebrain of adult rats treated for 21 days with either haloperidol, clozapine or saline. The dopamine D1 receptors, labeled with [3H]SCH23390, increased in nucleus accumbens, latero-dorsal rostral neostria...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1023/a:1022405621365
更新日期：1998-01-01 00:00:00
abstract：:To clarify the molecular basis of the cytoprotective properties of immunophilin ligands (IPLs), the anti-apoptotic effects of IPLs were determined in human glioma U251 cells. GPI1046 and V10367, non-immunosuppressive IPLs (NI-IPLs), as well as FK506, an immunosuppressive IPL (I-IPL), had cytoprotective effects against...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1023/b:nere.0000029565.92587.25
更新日期：2004-08-01 00:00:00
abstract：:Alzheimer's disease (AD) is pathologically characterized by presence of senile plaques in the hippocampus, which are composed mainly of extracellular deposition of a polypeptide known as the beta amyloid, the Aβ. It has been demonstrated on numerous occasions that it was the deposition and aggregation of this Aβ pepti...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-012-0846-6
更新日期：2012-10-01 00:00:00
abstract：:Three peptides overlapping the tryptophan region of bovine CNS myelin basic protein were synthesized by the solid phase procedure of Merrifield. These were the nonapeptide H-Phe-Ser-Trp-Gly-Ala-Glu-Gly-Gln-Lys-OH, the octapeptide H-Ser-Trp-Gly-Ala-Glu-Gly-Gln-Lys-OH, and the heptapeptide H-Trp-Gly-Ala-Glu-Gly-Gln-Lys-...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00964458
更新日期：1980-01-01 00:00:00
abstract：:Remyelination promoting human IgMs effectively increase the number of myelinated axons in animal models of multiple sclerosis. Hence, they ultimately stimulate myelin production by oligodendrocytes (OLs); however, their exact mechanism of action remains to be elucidated, and in particular, it remains unclear whether t...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-018-2701-x
更新日期：2019-06-01 00:00:00
abstract：:The frontal cortex, hippocampus, and cerebellum of the Fischer 344 rat were examined for an age-dependent change in neuronal and non-neuronal binding. Clonazepam and Ro5-6669 displaceable [3H]diazepam binding were used as indicators of [3H]diazepam binding on neuronal and non-neuronal membranes, respectively. In both ...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00964927
更新日期：1983-09-01 00:00:00
abstract：:Effects of single and repeated doses of acrylamide on fast and slow axonal transport of radio labeled proteins following the injection of L-[4,5-3H] leucine have been studied in the optic system of male Sprague-Dawley rats. A single dose of acrylamide (100 mg/kg) had no effect, but higher concentrations (200-300 mg/kg...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00973750
更新日期：1990-06-01 00:00:00
abstract：:The objective of the present study was to investigate the effects of senescence on the binding characteristics of muscarinic receptors by using [3H]quinuclidinyl benzilate ([3H]QNB) and [3H]N-methylscopolamine ([3H]NMS) as ligands in young (3 months), middle-age (10 months) and old (24 months) male Fischer 344 rats. M...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00971637
更新日期：1988-12-01 00:00:00
abstract：:Neuropeptides are derived from large and inactive proteins which require endoproteolytic processing for the biosynthesis of the bioactive peptides. The maturation of pro-neuropeptide to neuropeptide is believed to be performed by ortholog pro-protein convertase EGL-3 in Caenorhabditis elegans (C. elegans). Furthermore...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-018-2636-2
更新日期：2018-11-01 00:00:00
abstract：:The K-stimulated release of [3H]ACh from rat midbrain slices prelabeled by incubation with [3H]choline was dependent on extracellular Ca. Phenobarbital inhibited the K-stimulated [3H]ACh release and the IC50 was equal to that found for K-stimulated endogenous ACh release. These results support the suggestion that barb...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00964710
更新日期：1980-07-01 00:00:00
abstract：:Hippocampal cells dissociated from 5-day-old rat pups were grown in a suitable chemically defined basal medium, supplemented or not with 3,3',5-triiodo-L-thyronine (T3), [Arg8]-vasopressin (AVP), or both, at different concentrations. Four days after plating, neuron-like cells began to degenerate drastically in the bas...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00965924
更新日期：1989-10-01 00:00:00
abstract：:The activity of gamma-glutamyltransferase localized in isolated brain synaptic membranes- and microvessels-enriched fractions was assayed after treatment of rats with either phenobarbital or ethanol. Phenobarbital increased the activity of gamma-glutamyltransferase in microvessels, without alteration of synaptic membr...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00993245
更新日期：1987-04-01 00:00:00
abstract：:Agonist occupancy of muscarinic cholinergic receptors in human SH-SY-5Y neuroblastoma cells elicited two kinetically distinct phases of phosphoinositide hydrolysis when monitored by either an increased mass of inositol 1,4,5-trisphosphate, or the accumulation of a total inositol phosphate fraction. Within 5s of the ad...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00971329
更新日期：1994-05-01 00:00:00
abstract：:Fecal incontinence and constipation still remain the major complications after procedures for anorectal malformations (ARMs). Previous studies have demonstrated a decrease of neural cell in lumbosacral spinal cord of ARMs patients and rat models. However, the underlying mechanism remains elusive. In this study, the ne...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-017-2354-1
更新日期：2017-11-01 00:00:00
abstract：:Tumor Necrosis Factor Receptor Super Family 6 gene (TNFRSF6), also known as FAS, encodes the Fas antigen, a cell surface receptor mediating cell apoptosis, situated on chromosome 10q located near the region of linkage to sporadic Alzheimer's disease (sAD). FAS levels have been reported elevated in the brain of AD pati...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-007-9329-6
更新日期：2007-09-01 00:00:00
abstract：:Eclalbasaponin II derived from Eclipta prostrata L. (Asteraceae) has been reported to have anti-fibrotic, anti-bacterial and autophagic activities, but its effect on cognitive function has not been investigated. We studied the effect of eclalbasaponin II on cholinergic blockade-induced memory impairment in mice using ...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-017-2430-6
更新日期：2018-02-01 00:00:00
abstract：:In order to develop a simplified method for long-term primary culture of highly-pure rat embryonic hippocampal neurons of low-density (10(3) cells/cm(2)), we optimized and modified conventional culturing methods. The modifications of our simplified method include: (1) combinational application of two growth substrates...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-010-0189-0
更新日期：2010-09-01 00:00:00
abstract：:The ketone body, β-hydroxybutyrate (βOHB), is metabolised by the brain alongside the mandatory brain fuel glucose. To examine the extent and circumstances by which βOHB can supplement glucose metabolism, we studied guinea pig cortical brain slices using increasing concentrations of [U-13C]D-βOHB in conjunction with [1...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-017-2228-6
更新日期：2017-06-01 00:00:00
abstract：:The number of c-Fos protein-like immunoreactive (c-Fos-IR) neurons in the spinal dorsal horn evoked by noxious stimulation was previously shown to be increased following peripheral nerve injury, and this increase was proposed to reflect the neuropathic pain state. The aim of this study was to investigate whether anoma...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-014-1484-y
更新日期：2015-03-01 00:00:00
abstract：:Cysteinyl leukotrienes (CysLTs) are potent pro-inflammatory and immune modulating lipid mediators involved in inflammatory diseases and were boosted in human brain after acute phase of cerebral ischemia. The antagonism of CysLTs receptors may offer protection against ischemic damage. Therefore it seemed interesting to...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/s11064-014-1478-9
更新日期：2015-01-01 00:00:00
abstract：:The experiments reported in this paper address the hypothesis that [3H]leucine enkephalin labels both mu and delta receptors. As reported by other workers, this peptide dissociates from rat brain membranes in a biphasic manner. This is consistent with a two site binding model which hypothesizes that the peptide labels...
journal_title：Neurochemical research
pub_type： 杂志文章
doi：10.1007/BF00963918
更新日期：1983-02-01 00:00:00
