Abstract：
:Autophagy is a lysosomal degradation pathway, which is essential for cell survival, proliferation, differentiation and homeostasis. It is well known that beta-amyloid (Aβ) aggregation is one of key characteristics for Alzheimer's disease (AD), which triggers a complex pathological cascade, leading to neurodegeneration. Recent studies have shown that Aβ peptide is generated from amyloid β precursor protein (APP) during autophagic turnover of APP-rich organelles by autophagy. Aβ generation during normal autophagy is subsequently degraded by lysosomes. Curcumin, a nature plant extraction, has been reported to inhibit the generation and deposition of Aβ; however, the underlying mechanisms are not fully understood yet. In the present study, we reported that curcumin treatment not only attenuated cognitive impairment detected by Morris water maze test, but also inhibited the generation of Aβ investigated by immunohistochemistry in APP/PS1 double transgenic AD mice. Moreover, curcumin induced autophagy in the mice, evidenced by LC3 immunofluorescence analysis and western blot assays on LC3. Furthermore, we found that curcumin significantly decreased the expression of Phosphatidylinositol 3-Kinase (PI3K), phosphorylated Akt and rapamycin (mTOR) at protein levels, respectively. Taken together, our data suggests that curcumin inhibits Aβ generation and induces of autophagy by downregulating PI3K/Akt/mTOR signaling pathway, and further shows a neuroprotective effect. Meanwhile curcumin might be a candidate neuroprotective agent for AD patients treatment by inducing autophagy.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Wang C,Zhang X,Teng Z,Zhang T,Li Ydoi
10.1016/j.ejphar.2014.06.051subject
Has Abstractpub_date
2014-10-05 00:00:00pages
312-20eissn
0014-2999issn
1879-0712pii
S0014-2999(14)00502-0journal_volume
740pub_type
杂志文章abstract：:Glucocorticoids can reverse hemodynamic disturbances and dependence on catecholamines in septic shock. The relevant beneficial mechanisms of steroids in septic shock are unknown, although inducible nitric oxide synthase could account for them. The aim of this study was to compare the effects of dexamethasone, a glucoc...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(03)02035-1
更新日期：2003-08-15 00:00:00
abstract：:A mixture of dexamphetamine and chlordiazepoxide induces hyperactivity in both mice and rats. This type of hyperactivity has been proposed as an animal model of mania. Magnesium valproate itself had little influence on the activity of normal mice and rats. Acute pretreatment of mice with magnesium valproate (75-300 mg...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90266-k
更新日期：1993-06-24 00:00:00
abstract：:The main aim of the study was to examine analgesic effects of the topical opioids and non-steroidal anti-inflammatory drugs (NSAIDs) in a radiant heat tail-flick nociception model. Also, we have tested whether the addition of lauric acid to propylene glycol improves skin permeation for the opioids and NSAIDs. We found...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2007.10.014
更新日期：2008-01-28 00:00:00
abstract：:The quantitative [14C]iodoantipyrine autoradiographic method was applied to study the effects of acute administration of caffeine and L-phenylisopropyladenosine (LPIA) separately or in combination on local cerebral blood flow in the rat. After the injection of caffeine, cerebral blood flow rates were decreased in 13 o...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90165-3
更新日期：1990-04-25 00:00:00
abstract：:HgCl2 and mersalyl increased and later decreased both the spontaneous and evoked transmitter liberation at the frog neuromuscular junction. Lower concentration of HgCl2 exhibited only an inhibitory effect on transmitter release. These mercurials inhibited calcium transport of mitochondria and synaptosomal vesicles. Lo...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(78)90438-7
更新日期：1978-10-15 00:00:00
abstract：:In vivo effects of histidine and carnosine against diabetic deterioration in diabetic Balb/cA mice were studied. Histidine and carnosine at 0.5, 1 g/l were added into drinking water. After 4 weeks intake of these agents, the content of histidine and carnosine in plasma, heart and liver significantly elevated (P < 0.05...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2005.02.010
更新日期：2005-04-18 00:00:00
abstract：:Minocycline functions as a therapeutic drug in different diseases because of its cytoprotective properties. In the present study, we examined the potential of minocycline to decrease the islet loss in pre-transplantation culture stage. Pancreatic islets were isolated from the deceased donors and treated by 0, 2, 10, a...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2019.172518
更新日期：2019-09-05 00:00:00
abstract：:Neurokinins activate a series of tetrodotoxin (TTX)-insensitive rhythmic contractions of the rat isolated ureter. Field stimulation or capsaicin (1-3 microM) produced a transient inhibition of neurokinin-activated ureteral motility in preparations from control but not from capsaicin-pretreated (50 mg/kg s.c.) rats. Th...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(86)90068-3
更新日期：1986-07-31 00:00:00
abstract：:Cumulative dose-response curves of Ca2+-induced tension increments were studied in K+-depolarized helical strips of dog coronary arteries. Adenosine 10(-4) M reduced the Ca2+ sensitivity of the strips without altering the maximal tension with full Ca2+ activation. In contrast, acidosis of pH 7.05 significantly diminis...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(77)90212-6
更新日期：1977-01-21 00:00:00
abstract：:The ontogenesis of kappa-opioid receptors has been studied in the postnatal period from day 5 to day 30 using the highly selective kappa-site ligand [3H]U-69593 in binding studies. Analyses of saturation curves revealed a marked increase in the binding capacities between day 5 and day 10 with no further increment in t...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90157-2
更新日期：1990-01-03 00:00:00
abstract：:The adenosine A(2A) receptor in the basal ganglia is involved in the control of movement and plays a role in movement disorders such as Parkinsonism. Developing ligands to evaluate that receptor by noninvasive methods such as positron emission tomography has a high priority. In vitro radioligand binding guides the sel...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2009.06.025
更新日期：2009-08-15 00:00:00
abstract：:The effects of a serotonin (5-HT) releasing drug, p-chloroamphetamine, on plasma glucose levels were investigated in rats. p-Chloroamphetamine elicited a significant hyperglycemia. The hyperglycemic effects of p-chloroamphetamine were completely prevented by the 5-HT synthesis inhibitor, p-chlorophenylalanine. Prior a...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00639-6
更新日期：1998-10-23 00:00:00
abstract：:d-Lysergic acid diethylamide (LSD) produced dose-dependent contractions (EC50, 17.9 +/- 2.1 nM) on isolated ovine uterine artery of late pregnancy, which were competitively antagonized by ketanserin. The maximal contraction to LSD was 51% of the 5-HT response. LSD competitively antagonized (pA2 9.21) contractions prod...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90420-m
更新日期：1993-01-05 00:00:00
abstract：:In a medium containing 100 mM NaCl and 10 mM MgCl2, the binding of antagonists to rat myocardial muscarinic receptors is well described by the simple Langmuir isotherm. However, in low ionic strength media, while a small proportion of the sites (23%) display a small (2-3 fold) increase in antagonist affinity, the majo...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(81)90085-6
更新日期：1981-07-17 00:00:00
abstract：:Spontaneous electrical and mechanical activity was observed when single myocytes from guinea-pig hearts were loaded with sodium by direct intracellular application. Transient membrane depolarizations were found to be due to spontaneous inward currents (Isp). Both Isp and spontaneous contractions were abolished by 2',3...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90642-x
更新日期：1987-08-04 00:00:00
abstract：:Extravasation elicited in rat skin by antidromic electrical stimulation of the saphenous nerve was dose dependently inhibited by the intravenous (i.v.) application of the mu-opioid receptor agonists, morphine and [D-Ala2,Me-Phe4,Gly-ol5]enkephalin (DAGO), and the kappa-opioid receptor agonists (-)-U 50488H, (-)-ICI 19...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90233-8
更新日期：1993-05-12 00:00:00
abstract：:Dopamine (DA) was injected in the third brain ventricle of goats and the thermoregulatory effects were studied under different ambient conditions. The effects depended on dose, ambient conditions and cannula used. In the cold, there was a drop in body temperature, sometimes accompanied by suppression of shivering and ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(77)90153-4
更新日期：1977-05-01 00:00:00
abstract：:Two highly selective mu-opioid receptor agonists, endomorphin-1 and endomorphin-2, have been identified and postulated to be endogenous ligands for mu-opioid receptors. Intrathecal (i.t.) administration of endomorphin-1 and endomorphin-2 at doses from 0.039 to 5 nmol dose-dependently produced antinociception with the ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)01238-9
更新日期：2001-09-21 00:00:00
abstract：:The regulation of acetylcholine (ACh) lifetime by acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BuChE, EC 3.1.1.8) was evaluated in vitro in canine tracheal smooth muscle preparations. Selective inhibition of AChE by low concentrations of 1,5-bis(N-allyl-N,N-dimethyl-4-ammoniumphenyl)-pentane-3-on...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90772-i
更新日期：1991-11-19 00:00:00
abstract：:The effect of eliprodil on P-type Ca2+ channels was investigated in acutely dissociated rat Purkinje neurons, by using the whole-cell patch-clamp technique. Eliprodil inhibited in a reversible manner the omega-agatoxin-IVA-sensitive Ba2+ current elicited by step depolarizations from a -80 mV holding voltage (IC50 = 1....
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00511-0
更新日期：1995-12-27 00:00:00
abstract：:We previously reported the synthesis of three new opioid agonists as well as their in vitro and in vivo activity [Girón, R., Abalo, R., Goicoechea, C., Martín, M.I., Callado, L.F., Cano, C., Goya, P., Jagerovic, N. 2002. Synthesis and opioid activity of new fentanyl analogs. Life Sci. 71, 1023-1034]. One of them, N-[1...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.07.052
更新日期：2008-10-24 00:00:00
abstract：:To test whether polytherapy with two gamma-aminobutyric acid (GABA) -ergic drugs might be clinically relevant for epilepsy treatment, effects on spike and wave discharges, the fraction of time spent being behaviourally active, and the background electroencephalogram (EEG) during behavioural activity of vigabatrin (15-...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.05.027
更新日期：2004-07-14 00:00:00
abstract：:This study was designed to determine if the histamine H3 receptor agonist R-alpha-methylhistamine would play a role in modulation of sympathetically evoked mydriasis in anesthetized rats, and if so, to ascertain the specific receptor subtype(s) involved. Reproducible frequency-response curves of pupillary dilation wer...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)00977-3
更新日期：2001-05-04 00:00:00
abstract：:The antiparkinsonian agent l-deprenyl is metabolized to l-methamphetamine and l-amphetamine and, at higher doses, can facilitate the release and inhibit the reuptake of dopamine. Since l-deprenyl can affect dopamine release and reuptake it was important to evaluate it for cocaine-like discriminative stimulus effects. ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)90650-5
更新日期：1994-07-11 00:00:00
abstract：:We have assessed the capacity of two novel inhibitors to block cytokine-induced nitric oxide (NO) synthesis by macrophages and vascular smooth muscle cells, as well as NO production by the constitutive enzyme in central nervous system tissue. NG-Cyclopropyl-L-arginine selectively inhibited Ca2+/calmodulin-dependent NO...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90221-o
更新日期：1992-05-27 00:00:00
abstract：:The aims of the present study were to establish whether vasoactive intestinal polypeptide (VIP) could mobilize internally-stored Ca2+ and whether Ca2+ release could trigger Ca2+ influx from the extracellular space. Bovine pulmonary artery endothelial cells from an established cell line were loaded with fura-2/AM and c...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01315-0
更新日期：1997-11-27 00:00:00
abstract：:The effects of cyclic nucleotide analogs and related agents on the Ca2+ dependent action potentials of cultured rat aortic smooth muscle cells (reaggregates) were examined. The action potentials were elicited by electrical stimulation in the presence of tetraethylammonium (TEA, 5-15 mM). Superfusion of the aortic cell...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90003-3
更新日期：1987-11-24 00:00:00
abstract：:All-night spectral analysis of the sleep EEG was used to study the effect and after-effect of a single bedtime dose of flunitrazepam (2 mg), flurazepam (30 mg) or triazolam (0.5 mg) in healthy young males. In the night of drug treatment all 3 hypnotics reduced the EEG slow waves and enhanced the activity in the freque...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(83)90622-2
更新日期：1983-04-22 00:00:00
abstract：:Type 2 diabetes mellitus (T2DM) is known to be associated with increased risk of cognitive impairment including Alzheimer disease. Recent studies have suggested an interaction between angiotensin II and N-methyl-d-aspartic acid (NMDA) glutamate receptors. We previously reported that stimulation of the angiotensin II t...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.12.015
更新日期：2014-02-05 00:00:00
abstract：:Rats isolated at 16--18 days of age showed after 10--12 months a complex behavioural syndrome in which locomotor activity was markedly increased when compared to that of group-housed controls. The hyperactivity of the socially deprived animals was selectively blocked by clinically effective antidepressants but not by ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(79)90293-0
更新日期：1979-11-16 00:00:00
