Abstract：
:During the last 20 years, an expanding body of research has elucidated the central role of amyloid precursor protein (APP) processing and amyloid beta peptide (Abeta) production in the risk, onset, and progression of the neurodegenerative disorder Alzheimer's disease (AD), the most common form of dementia. Ongoing research is establishing a greater level of detail for our understanding of the normal functions of APP, its proteolysis products, and the mechanisms by which this processing occurs. The importance of this processing machinery in normal cellular function, such as Notch processing, has revealed specific concerns about targeting APP processing for therapeutic purposes. Aspects of AD that are now well studied include direct and indirect genetic and other risk factors for AD, APP processing, and Abeta production. Emerging from these studies is the particular importance of the long form of Abeta, Abeta42. Elevated Abeta42 levels, as well as particularly the elevation of the ratio of Abeta42 to the shorter major form Abeta40, has been identified as important in early events in the pathogenesis of AD. The specific pathological importance of Abeta42 has drawn attention to seeking drugs that will selectively lower the levels of this peptide through reduced production or increased clearance while allowing normal protein processing to remain substantially intact. An increasing variety of compounds that modulate APP processing to reduce Abeta levels are being identified, some with Abeta42 selectivity. Such compounds are now reaching clinical evaluation to determine how they may be of benefit in the treatment of AD.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Findeis MAdoi
10.1016/j.pharmthera.2007.06.006subject
Has Abstractpub_date
2007-11-01 00:00:00pages
266-86issue
2eissn
0163-7258issn
1879-016Xpii
S0163-7258(07)00143-Xjournal_volume
116pub_type
杂志文章,评审abstract：:Pokeweed antiviral protein (PAP) is a ribosome-inactivating protein (RIP) that inactivates ribosomes by the removal of a single adenine from ribosomal RNA. The studies summarized in our review concern the nature and application of this novel therapeutic agent. We describe how researchers continue to elucidate the stru...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(92)90053-3
更新日期：1992-01-01 00:00:00
abstract：:Natural D-nucleosides are no longer the sole basis for designing effective antiviral analogues. Many antivirals with an opposite (L) configuration were reported, with lamivudine being the most notable example. In contrast, carbocyclic nucleoside analogues are significantly more enantioselective, and enantiomers with a...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(99)00062-5
更新日期：2000-03-01 00:00:00
abstract：:The coronavirus disease 2019 (COVID-19) pandemic is caused by a newly emerged coronavirus (CoV) called Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). COVID-19 patients with cardiovascular disease (CVD) comorbidities have significantly increased morbidity and mortality. The use of angiotensin-converting ...
journal_title：Pharmacology & therapeutics
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doi：10.1016/j.pharmthera.2020.107628
更新日期：2020-11-01 00:00:00
abstract：:Initially regarded as "epigenetic modifiers" acting predominantly through chromatin remodeling via histone acetylation, HDACIs, alternatively referred to as lysine deacetylase or simply deacetylase inhibitors, have since been recognized to exert multiple cytotoxic actions in cancer cells, often through acetylation of ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
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更新日期：2014-09-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
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更新日期：2007-11-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2003.10.001
更新日期：2004-01-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
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更新日期：2012-01-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2015.08.002
更新日期：2015-11-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(95)00002-x
更新日期：1995-05-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
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更新日期：1985-01-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 历史文章,杂志文章,评审
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更新日期：1987-01-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2019.04.005
更新日期：2019-08-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(92)90005-k
更新日期：1992-01-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(95)02044-6
更新日期：1996-01-01 00:00:00
abstract：:Patients of congenital diseases such as Down syndrome (DS) and Duchenne muscular dystrophy (DMD) have abnormalities in their chromosomes and/or genes. Therefore, it has been considered that drug treatments can serve to do little for these patients more than to patch over each symptom temporarily when it arises. Althou...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2012.02.001
更新日期：2012-06-01 00:00:00
abstract：:G protein-coupled receptors (GPCR) interact not only with heterotrimeric G proteins but also with accessory proteins called GPCR interacting proteins (GIP). These proteins have important functions. They are implicated in GPCR targeting to specific cellular compartments, in their assembling into large functional comple...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2004.06.004
更新日期：2004-09-01 00:00:00
abstract：:Thromboxane A(2) (TXA(2)), an unstable arachidonic acid metabolite, elicits diverse physiological/pathophysiological actions, including platelet aggregation and smooth muscle contraction. TXA(2) has been shown to be involved in allergies, modulation of acquired immunity, atherogenesis, neovascularization, and metastas...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2008.01.001
更新日期：2008-04-01 00:00:00
abstract：:Conditional gene knockout represents an extremely powerful approach to study the function of single genes in the nervous system. The Cre-LoxP system is the most advanced technology for spatial and temporal control of genetic inactivation, and there is rapid progress using this methodology in neuroscience research. In ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2006.12.003
更新日期：2007-03-01 00:00:00
abstract：:Artemisinins are a unique class of antimalarial drugs with significant potential for drug repurposing for a wide range of diseases including cancer. Cancer is a leading cause of death globally and the majority of cancer related deaths occur in Low and Middle Income Countries (LMICs) where conventional treatment option...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107706
更新日期：2020-12-01 00:00:00
abstract：:Stroke is a major clinical problem, and acute pharmacological intervention with neuroprotective agents has so far been unsuccessful. Recently, there has been considerable interest in the potential therapeutic benefit of nitrone-derived free radical trapping agents as neuroprotective agents. Nitrone compounds have been...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2003.07.003
更新日期：2003-12-01 00:00:00
abstract：:Recent evidence indicates that ethanol modulates the function of specific intracellular signaling cascades, including those that contain cyclic adenosine 3', 5'-monophosphate (cAMP)-dependent protein kinase A (PKA), protein kinase C (PKC), the tyrosine kinase Fyn, and phospholipase D (PLD). In some cases, the specific...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.07.004
更新日期：2006-01-01 00:00:00
abstract：:Purinergic signaling, mediated mainly by G protein-coupled P2Y receptors (P2YRs), is now attracting attention as a new therapeutic target for preventing or treating cardiovascular diseases. Observations using mice with genetically modified P2YRs and/or treated with a pharmacological P2YR inhibitor have helped us under...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2017.06.010
更新日期：2017-12-01 00:00:00
abstract：:QT interval prolongation, corrected for heart rate (QTc), either spontaneous or drug-induced, is associated with an increased risk of torsades de pointes and sudden death. Women have longer QTc than men and are at higher risk of torsades de pointes, particularly during post-partum and the follicular phase. Men with pe...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
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更新日期：2016-11-01 00:00:00
abstract：:Diabetes is a debilitating disease characterized by chronic hyperglycemia and is often associated with obesity. With diabetes and obesity incidence on the rise, it is imperative to develop novel therapeutics that will not only lower blood glucose levels, but also combat the associated obesity. The G protein-coupled re...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2012.05.009
更新日期：2012-09-01 00:00:00
abstract：:The receptors involved in bitter taste perception (bitter taste receptors--T2Rs) constitute a family of G-protein-coupled receptors, of which around 29 subtypes have been identified in humans. T2R expression was initially thought to be confined to the oral cavity but has recently been described in a range of other tis...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2015.08.001
更新日期：2015-11-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2007.03.005
更新日期：2007-08-01 00:00:00
abstract：:Administration of antidepressant drugs to rodents appears to decrease 5-HT2 receptor function while transmission through postsynaptic 5-HT1 receptor synapses may be enhanced. Antidepressant drugs also alter 5-HT mechanisms in humans; some of these changes are congruent with effects noted in animal studies. Thus certai...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(90)90033-x
更新日期：1990-01-01 00:00:00
abstract：:Nongenomic estrogen signaling pathways involve extranuclear estrogen receptors or function independently from estrogen receptors. These pathways participate in neuroprotection elicited by the hormone. Additional nongenomic neuroprotective effects are attributable to antioxidant and antiinflammatory actions of estrogen...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2007.01.006
更新日期：2007-04-01 00:00:00
abstract：:Phosphorothioate (PS) oligodeoxynucleotides are relatively nuclease resistant, water soluble analogs of phosphodiester (PO) oligodeoxynucleotides. These molecules are chiral but still hybridize well to their RNA targets. While considered for use as in vivo anti-sense inhibitors of gene expression, their biology, espec...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(91)90032-h
更新日期：1991-12-01 00:00:00
abstract：:Evidence from experimental and clinical studies suggests the involvement of the endogenous opioid system in several neurologic and psychiatric disorders (Alzheimer's, Huntington's and Parkinson's diseases, drug-induced movement disorders, Gilles de la Tourette syndrome, stroke, ischemia, brain and spinal cord injury, ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(90)90026-x
更新日期：1990-01-01 00:00:00
