Abstract：
:The prescribed drugs for treatment of cognitive deficits in Alzheimer's disease (AD) patients are regarded as symptomatic drugs. Effective disease modifying therapies are not yet prescribed in AD patients. Three major hallmarks of AD (e.g. cholinergic hypofunction, Aβ and tau neuropathologies) are closely linked raising the expectation that restoring the cholinergic hypofunction to normal, in particular via selective activation of M1 muscarinic receptors, may alter the onset or progression of AD dementia. This review is focused mainly on modulation of amyloid precursor processing and Aβ levels in the brain via cholinergic treatment strategies based on M1 muscarinic agonists versus other cholinergic treatments (e.g. cholinesterase inhibitors prescribed for treatment of AD, M2 antagonists and nicotinic agonists). Advantages and potential drawbacks of these treatment modalities are reviewed versus the notion that due to an elusive etiology of AD, future disease modifiers should address comprehensively most of these AD hallmarks (e.g. Aβ pathology, tau and tangle pathologies, as well as the cholinergic hypofunction and cognitive impairments). This major requirement may be fulfilled with M1-selective muscarinic agonists and less with other reviewed cholinergic treatments.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Fisher Adoi
10.1111/j.1471-4159.2011.07507.xsubject
Has Abstractpub_date
2012-01-01 00:00:00pages
22-33eissn
0022-3042issn
1471-4159journal_volume
120 Suppl 1pub_type
杂志文章,评审abstract：:The ontogeny of chick brain and heart ventricle calcium antagonist binding sites was determined, using [3H]nitrendipine ([3H]NDP), as the ligand. The binding of [3H]NDP to adult heart and brain was kinetically very similar, with the former displaying a KD of 0.28 +/- 0.02 nM and a Bmax of 138 +/- 17 fmol/mg protein, a...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1984.tb02792.x
更新日期：1984-05-01 00:00:00
abstract：:Postmortem changes in catecholamines, indoleamines, and their metabolites in rat brain regions following decapitation were determined by LCEC. In the three regions studied neurotransmitter levels declined after decapitation, whereas the metabolite levels increased. Microwave irradiation at 10 kW rapidly inactivated br...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1985.tb04083.x
更新日期：1985-09-01 00:00:00
abstract：:The extracellular regulated kinases (ERK) 1 and ERK2 are members of mitogen-activated protein (MAP) kinase family that play an important role in transducing extracellular signals to the nucleus and have been implicated in a broad spectrum of biological responses. To test the hypothesis that MAP kinases may be involved...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2001.00300.x
更新日期：2001-05-01 00:00:00
abstract：:Axonal degeneration is a key component of many neurodegenerative diseases. Injured axons undergo a program of self-destruction termed Wallerian degeneration that is an active, well-regulated process. The pathways leading to axon fragmentation are uncharacterized, but experiments with wld(s) mutant mice led to the disc...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2009.06002.x
更新日期：2009-04-01 00:00:00
abstract：:The cellular localization of the two forms of catechol-O-methyltransferase (COMT) was investigated by measuring their activities in rat striatum following unilateral stereotaxic injection of kainic acid, which causes degeneration of striatal neurons followed by proliferation of astroglial cells. Membrane-bound COMT ac...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1983.tb12673.x
更新日期：1983-01-01 00:00:00
abstract：:The proportion of major depressive disorder (MDD) patients around the world has increased remarkably. Although many studies of MDD have been conducted based on classic hypotheses, like alteration of the hypothalamic-pituitary-adrenal axis or monoamine neurotransmitters, the mechanisms underlying MDD remain unclear. Ai...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.14641
更新日期：2019-06-01 00:00:00
abstract：:The effect of angiotensin (Ang) IV, an inhibitor of insulin-regulated aminopeptidase (IRAP), on extracellular dopamine levels in the striatum of freely moving rats was examined using in vivo microdialysis. The Ang IV was administered locally in the striatum through the microdialysis probe. A concentration-dependent (1...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2004.02600.x
更新日期：2004-09-01 00:00:00
abstract：:Changes in cellular energetic and metabolic parameters were analyzed at several time points during apoptosis of differentiated PC12 cells following removal of nerve growth factor (NGF). As approximately 60% of the population died during the period of study (24 h), most of the measured metabolic indicators declined ove...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1995.65041721.x
更新日期：1995-10-01 00:00:00
abstract：:Here we report the cloning of two cDNAs, Snf2h and Snf2l, encoding the murine members of the Imitation Switch (ISWI) family of chromatin remodeling proteins. To gain insight into their function we examined the spatial and temporal expression patterns of Snf2h and Snf2l during development. In the brain, Snf2h is preval...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2001.00324.x
更新日期：2001-05-01 00:00:00
abstract：:Carbamylcholine stimulated phospholipase C activity in astrocytes in primary culture from the mesencephalon but not from the striatum or cerebral cortex of the mouse embryo. An alpha 1-adrenergic-mediated response was observed in all astrocyte populations. 2-Chloroadenosine potentiated the alpha 1-adrenergic response ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1989.tb02551.x
更新日期：1989-03-01 00:00:00
abstract：:The proinflammatory cytokine interleukin 1beta (IL-1beta), acting at IL-1R1 receptors, affects neuronal signaling under both physiological and pathophysiological conditions. The molecular mechanism of the rapid synaptic actions of IL-1beta in neurons is not known. We show here that within minutes of IL-1beta exposure,...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2006.03951.x
更新日期：2006-09-01 00:00:00
abstract：:The effects of gamma-aminobutyric acid (GABA) on the extracellular levels of taurine and on excitability in the dentate gyrus were studied in anesthetized rats by the dialytrode technique. The dentate gyrus was perfused by means of a dialytrode with Krebs-Ringer-bicarbonate or GABA solutions. Amino acid contents in pe...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1985.tb12913.x
更新日期：1985-03-01 00:00:00
abstract：:Calf brain 3'-phosphoadenosine 5'-phosphosulfate (PAPS):proteoheparan sulfate (PHS) N-sulfotransferase activity is solubilized by extracting salt-washed microsomes with 1% Cutscum. A protocol is described for the partial purification of the sulfotransferase activity utilizing: (1) diethylaminoethyl (DEAE)-Sephacel, (2...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1988.tb04839.x
更新日期：1988-07-01 00:00:00
abstract：:Alzheimer's disease is characterized neuropathologically by the presence of neuritic and amyloid plaques, vascular amyloid, and neurofibrillary tangles in specific brain areas. The main constituent of amyloid deposits is amyloid beta protein, a 40-42 amino acid proteolytic product of the amyloid beta-precursor protein...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1996.66052011.x
更新日期：1996-05-01 00:00:00
abstract：:This study evaluated the developmental gene and protein expression of proton-coupled oligopeptide transporters (POTs: peptide transporter, PepT1 and PepT2; peptide-histidine transporter, PhT1 and PhT2) in different regions of rodent brain, and the age-dependent uptake of a POT substrate, glycylsarcosine (GlySar), in b...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.12687
更新日期：2014-06-01 00:00:00
abstract：:Brain trauma was induced in mice using a closed head injury (CHI) model. At 1, 6 or 24 h after trauma, brains were dissected into the cortex, striatum and hippocampus. Changes in levels of processed X-box protein 1 (xbp1), glucose-regulated protein 78 (grp78), growth arrest and DNA damage-inducible gene 153 (gadd153) ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2003.02218.x
更新日期：2004-02-01 00:00:00
abstract：:Spinocerebellar ataxia 1 (SCA1) is a dominantly inherited neurodegenerative disease associated with progressive ataxia resulting from the loss of cerebellar Purkinje cells (PCs) and neurons in the brainstem. In PCs of SCA1 transgenic mice, the disease causing ataxin-1 protein mediates the formation of S100B containing...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2010.06791.x
更新日期：2010-08-01 00:00:00
abstract：:The metabolic pathway of inositol phospholipids represents a series of synthetic and hydrolytic reactions with inositol as a by-product. Hence, the rate of [3H]inositol release from prelabeled phospholipids can be used as a reflection of activity of this pathway. In the frog sympathetic ganglion prelabeled with [3H]in...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1989.tb02524.x
更新日期：1989-03-01 00:00:00
abstract：:Presynaptic nicotinic acetylcholine receptors on striatal nerve terminals modulate the release of dopamine. We have compared the effects of a number of nicotinic agonists and antagonists on a perfused synaptosome preparation preloaded with [3H]dopamine. (-)-Nicotine, acetylcholine, and the nicotinic agonists cytisine ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1990.tb02341.x
更新日期：1990-03-01 00:00:00
abstract：:Agonist activation of the delta-opioid receptor leads to internalization via G betagamma recruitment of G protein coupled receptor kinase-2, which phosphorylates the receptor at several sites, including Ser363, allowing beta-arrestin binding and localization to clathrin coated pits. Using human embryonic kidney cells ...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2009.06082.x
更新日期：2009-06-01 00:00:00
abstract：:The recycling of synaptic vesicles in nerve terminals involves multiple steps, underlies all aspects of synaptic transmission, and is a key to understanding the basis of synaptic plasticity. The development of styryl dyes as fluorescent molecules that label recycling synaptic vesicles has revolutionized the way in whi...
journal_title：Journal of neurochemistry
pub_type： 杂志文章,评审
doi：10.1046/j.1471-4159.1999.0732227.x
更新日期：1999-12-01 00:00:00
abstract：:In cerebellar granule cells, the mitogen-activated protein kinase (MAPK) or extracellular signal-regulated kinase (ERK) cascade mediates multiple functions, including proliferation, differentiation, and survival. In these cells, ERKs are activated by diverse stimuli, including cyclic adenosine monophosphate (cAMP), pi...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2006.04390.x
更新日期：2007-04-01 00:00:00
abstract：:Accumulations of the neuropeptides substance P (SP), somatostatin (ST), and vasoactive intestinal polypeptide (VIP) proximal to a crush in the cervical vagus nerve of the rat have been measured using sensitive radioimmunoassays. Each of the peptides was rapidly transport towards the peripheral terminals of vagal affer...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1980.tb04627.x
更新日期：1980-01-01 00:00:00
abstract：:The effects of treatment with the anti-convulsant agents, lamotrigine and riluzole were compared with gabapentin in a rat experimental model of neuropathic pain. Rats were treated intraperitoneally, with gabapentin (30, 100 and 300 mg/kg), lamotrigine (2, 10 and 50 mg/kg) or riluzole (6 and 12 mg/kg) prior to, and eve...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2006.04304.x
更新日期：2007-03-01 00:00:00
abstract：:Dopaminergic neurons in cultures of dissociated cells from fetal rat mesencephalon were exposed to the principal metabolite of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl-4-phenyl-pyridinium ion (MPP+), and several of its structural analogues. At concentrations between 0.01 and 0.1 mic...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1988.tb02500.x
更新日期：1988-06-01 00:00:00
abstract：:Glutamate is the major excitatory transmitter in the vertebrate brain and its extracellular levels are tightly regulated to prevent excitotoxic effects. The Na(+)-dependent glutamate/aspartate transporter GLAST/EAAT1 is regulated in the short and in the long term by glutamate. A receptors-independent change in its mem...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.2007.04517.x
更新日期：2007-05-01 00:00:00
abstract：:To investigate if the prevention of disulfide bond formation affects the intracellular transport, sorting, and processing of a distinct set of neuroendocrine proteins in the regulated secretory pathway, we have treated Xenopus intermediate pituitaries with the thiol-reducing agent dithiothreitol. Pulse-chase incubatio...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.1998.71010402.x
更新日期：1998-07-01 00:00:00
abstract：:Before this study, the human norepinephrine transporter (hNET) was the only member of the biogenic amine neurotransmitter transporter family that had not been demonstrated to be a functional homo-oligomer. Here, using two forms of the transporter, I155C and hNET-myc, with distinct antigenicity and inhibitor sensitivit...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1046/j.1471-4159.2003.01793.x
更新日期：2003-06-01 00:00:00
abstract：:The subcellular distribution of the ectoenzyme, 5'-nucleotidase, in cerebral cortex and cerebellum of the rat was studied both biochemically and cytochemically. The fractions were characterized biochemically by marker enzymes. The localization of 5'-nucleotidase activity was also investigated cytochemically in the mye...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/j.1471-4159.1984.tb12832.x
更新日期：1984-10-01 00:00:00
abstract：:Therapy of malignant glioma relies on treatment with the O6 -methylating agent temozolomide (TMZ) concomitant with ionizing radiation followed by adjuvant TMZ. For the treatment of recurrences, DNA chloroethylating drugs are also used. The main killing lesion induced by these drugs is O6 -alkylguanine. Since this dama...
journal_title：Journal of neurochemistry
pub_type： 杂志文章
doi：10.1111/jnc.14262
更新日期：2018-01-01 00:00:00
