Abstract：
:Alzheimer's disease (AD) is the most common cause of dementia, clinically characterized by loss of memory and progressive deficits in different cognitive domains. An emerging disease-modifying approach to face the multifactorial nature of AD may be represented by the development of Multi-Target Directed Ligands (MTDLs), i.e., single compounds which may simultaneously modulate different targets involved in the neurodegenerative AD cascade. The structure of tacrine, an acetylcholinesterase (AChE) inhibitor (AChEI), has been widely used as scaffold to provide new MTDLs. In particular, its homodimer bis(7)tacrine represents an interesting lead compound to design novel MTDLs. Thus, in the search of new rationally designed MTDLs against AD, we replaced the heptamethylene linker of bis(7)tacrine with the structure of cystamine, leading to cystamine-tacrine dimer. In this study we demonstrated that the cystamine-tacrine dimer is endowed with a lower toxicity in comparison to bis(7)tacrine, it is able to inhibit AChE, butyrylcholinesterase (BChE), self- and AChE-induced beta-amyloid aggregation in the same range of the reference compound and exerts a neuroprotective action on SH-SY5Y cell line against H(2)O(2)-induced oxidative injury. The investigation of the mechanism of neuroprotection showed that the cystamine-tacrine dimer acts by activating kinase 1 and 2 (ERK1/2) and Akt/protein kinase B (PKB) pathways. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Minarini A,Milelli A,Tumiatti V,Rosini M,Simoni E,Bolognesi ML,Andrisano V,Bartolini M,Motori E,Angeloni C,Hrelia Sdoi
10.1016/j.neuropharm.2011.10.007subject
Has Abstractpub_date
2012-02-01 00:00:00pages
997-1003issue
2eissn
0028-3908issn
1873-7064pii
S0028-3908(11)00462-Xjournal_volume
62pub_type
杂志文章abstract：:The exact role of opioid receptor signaling in mediating voluntary wheel running is unclear. To provide additional understanding, female rats selectively bred for motivation of low (LVR) versus high voluntary running (HVR) behaviors were used. Aims of this study were 1) to identify intrinsic differences in nucleus acc...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2015.05.022
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abstract：:Behavioral sensitization, or augmented locomotor response to successive drug exposures, results from neuroadaptive changes contributing to addiction. Both the medial prefrontal cortex (mPFC) and ventral tegmental area (VTA) influence behavioral sensitization and display increased immediate-early gene and BDNF expressi...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2011.04.026
更新日期：2011-09-01 00:00:00
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journal_title：Neuropharmacology
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doi：10.1016/j.neuropharm.2008.03.016
更新日期：2008-06-01 00:00:00
abstract：:P2Y1 receptors mediate nerve mediated purinergic inhibitory junction potentials (IJP) and relaxations in the gastrointestinal (GI) tract in a wide range of species including rodents and humans. A new P2Y1 antagonist, with a non-nucleotide structure, BPTU, has recently been described using X-ray crystallography as the ...
journal_title：Neuropharmacology
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doi：10.1016/j.neuropharm.2016.07.033
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2016.01.014
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2013.05.017
更新日期：2013-10-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2017.01.022
更新日期：2017-05-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(92)90133-a
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journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2019.107790
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(11)80015-8
更新日期：1991-12-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2007.08.010
更新日期：2007-11-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(84)90120-5
更新日期：1984-09-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/0028-3908(94)00151-h
更新日期：1995-02-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(84)90201-6
更新日期：1984-03-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2008.08.039
更新日期：2008-12-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2017.11.002
更新日期：2018-02-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2013.08.004
更新日期：2013-12-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2014.07.006
更新日期：2014-11-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2017.03.003
更新日期：2017-05-15 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章,评审
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更新日期：2004-12-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2007.03.015
更新日期：2007-06-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2017.07.021
更新日期：2018-07-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(87)90142-0
更新日期：1987-06-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(82)90020-x
更新日期：1982-05-01 00:00:00
abstract：:Calcium currents in the inferior colliculus (IC) are thought to play an important role in ethanol withdrawal hyperexcitability. Here, we report on the modulation of Ca(2+) channel currents in acutely dissociated IC neurons of rats, exhibiting higher incidence of audiogenic seizures when subjected to ethanol withdrawal...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(03)00191-6
更新日期：2003-09-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2006.01.012
更新日期：2006-08-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2004.04.016
更新日期：2004-09-01 00:00:00
abstract：:We have previously demonstrated that an acute dose of Δ9-tetrahydrocanninbinol (THC), administered prior to extinction learning, facilitates later recall of extinction learning and modulates the underlying neural circuitry, including the ventromedial prefrontal cortex (vmPFC), hippocampus (HPC), and amygdala (AMYG). I...
journal_title：Neuropharmacology
pub_type： 杂志文章,随机对照试验
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更新日期：2018-12-01 00:00:00
abstract：:These experiments examined the effects of lithium and imipramine on the regulation by norepinephrine in vivo of (Na+, K+)-ATPase in brain and heart. The binding of ouabain and the activity of K+-phosphatase were used as indices of (Na+, K+)-ATPase. In the cerebral cortex, imipramine prevented, and lithium reduced, the...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(88)90042-1
更新日期：1988-03-01 00:00:00
