Abstract:
:Despite the success of combined antiretroviral therapy, more than half of HIV-1-infected patients in the USA show HIV-associated neurological and neuropsychiatric deficits. This is accompanied by anatomical and functional alterations in vulnerable brain regions of the mesocorticolimbic and nigrostriatal systems that regulate cognition, mood and motivation-driven behaviors, and could occur at early stages of infection. Neurons are not infected by HIV, but HIV-1 proteins (including but not limited to the HIV-1 trans-activator of transcription, Tat) induce Ca(2+) dysregulation, indicated by abnormal and excessive Ca(2+) influx and increased intracellular Ca(2+) release that consequentially elevate cytosolic free Ca(2+) levels ([Ca(2+)]in). Such alterations in intracellular Ca(2+) homeostasis significantly disturb normal functioning of neurons, and induce dysregulation, injury, and death of neurons or non-neuronal cells, and associated tissue loss in HIV-vulnerable brain regions. This review discusses certain unique mechanisms, particularly the over-activation and/or upregulation of the ligand-gated ionotropic glutamatergic NMDA receptor (NMDAR), the voltage-gated L-type Ca(2+) channel (L-channel) and the transient receptor potential canonical (TRPC) channel (a non-selective cation channel that is also permeable for Ca(2+)), which may underlie the deleterious effects of Tat on intracellular Ca(2+) homeostasis and neuronal hyper-excitation that could ultimately result in excitotoxicity. This review also seeks to provide summarized information for future studies focusing on comprehensive elucidation of molecular mechanisms underlying the pathophysiological effects of Tat (as well as some other HIV-1 proteins and immunoinflammatory molecules) on neuronal function, particularly in HIV-vulnerable brain regions.
journal_name
Curr Drug Targetsjournal_title
Current drug targetsauthors
Hu XTdoi
10.2174/1389450116666150531162212subject
Has Abstractpub_date
2016-01-01 00:00:00pages
4-14issue
1eissn
1389-4501issn
1873-5592pii
CDT-EPUB-67777journal_volume
17pub_type
杂志文章,评审abstract:BACKGROUND:The plant milk thistle and silymarin has been traditionally used as a natural remedy for the treatment of various ailments including neurological disorders such as Alzheimer's and Parkinson's disease and cerebral ischemia for over 2000 years. OBJECTIVE:In this article we review the neuroprotective effects o...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666161227125121
更新日期:2017-01-01 00:00:00
abstract::The development of novel T cell therapies to target leukemia has facilitated the translation of this approach for hematologic malignancies. Different methods of manufacturing leukemia-specific T cells have evolved, along with additional measures to increase the safety of this therapy. This is an overview of expanded T...
journal_title:Current drug targets
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doi:10.2174/1389450117666160209143529
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abstract::The CD6 molecule is a pan T cell marker involved in T cell regulation. Although CD6 expression has been correlated with human autoimmune diseases, only a few therapeutic approaches are exploring this molecule as target in the clinic. The biological functions and mechanisms of actions of CD6 have not been definitively ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
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journal_title:Current drug targets
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doi:10.2174/1389450121666201020154033
更新日期:2020-10-20 00:00:00
abstract::Hypertension is usually associated with deficient nitric oxide (NO) bioavailability, and therefore stimulating NO activity is an important antihypertensive strategy. Recently, many studies have shown that both nitrite and nitrate anions are not simple products of NO metabolism and indeed may be reduced back to NO. Whi...
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pub_type: 杂志文章,评审
doi:10.2174/1389450119666180816120816
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journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450115666140321120635
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abstract::HIV-1 replicates by infecting new target cells either as cell-free viral particle or, much more efficiently, via cell-to-cell viral transmission. Cell-mediated viral spread, in which the infected cell directly transfers the viral particles to target cells via cell-cell contacts, in vitro is up to three orders of magni...
journal_title:Current drug targets
pub_type: 杂志文章
doi:
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journal_title:Current drug targets
pub_type: 杂志文章,评审
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journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666160112112640
更新日期:2016-01-01 00:00:00
abstract::The Wnt signaling pathway has important functions in development, tissue homeostasis, and regeneration. Deregulation of canonical Wnt/beta-catenin signaling is frequently found in various human cancers, particularly in colorectal cancer, and non-canonical Wnt signaling pathways also have been implicated in neoplasia. ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945008784911769
更新日期:2008-07-01 00:00:00
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journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945007780830764
更新日期:2007-06-01 00:00:00
abstract::Recently, the presence of functional interaction between the opioid and cannabinoid system has been shown in various pharmacological responses. Although there is an increasing interest for the feasible therapeutic application of a co-administration of cannabinoids and opioids in some disorders (i.e. to manage pain, to...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945010790980367
更新日期:2010-04-01 00:00:00
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journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945006778226660
更新日期:2006-09-01 00:00:00
abstract::Multi-target drugs against particular multiple targets get better protection, resistance profiles and curative influence by cooperative rules of a key beneficial target with resistance behavior and compensatory elements. Computational techniques can assist us in the efforts to design novel drugs (ligands) with a prefe...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666160101120822
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Gabapentin and pregabalin inhibit Ca(2+) currents via high-voltage-activated channels containing the alpha2delta-1 subunit, reducing neurotransmitter release and attenuating the postsynaptic excitability. They are antiepileptic drugs successfully used also for the chronic pain treatment. A large number of cl...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945009788982513
更新日期:2009-08-01 00:00:00
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journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945006775270213
更新日期:2006-01-01 00:00:00
abstract::Aberrant activation of receptor-tyrosine kinase c-Met/HGF pathway is shown to be associated with cell proliferation, invasion, metastasis and poor-prognosis in several tumor types, including upper gastrointestinal-malignancies. The interaction of c-Met with multiple signalling-pathways involved in tumorigenic-properti...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450115666141107105456
更新日期:2014-01-01 00:00:00
abstract::The fibrinolytic system consists of a balance between rates of plasminogen activation and fibrin degradation, both of which are finely regulated by spatio-temporal mechanisms. Three distinct inhibitors of the fibrinolytic system that differently regulate these two steps are plasminogen activator inhibitor type-1 (PAI-...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450120666190715102510
更新日期:2019-01-01 00:00:00
abstract::PDZ domains play an essential role in a number of cellular processes by facilitating protein scaffolding and assembly of protein complexes. These domains consist of 80 to 90 amino acids and are found to recognize short C-terminal sequences of target proteins. Protein complex formation between PDZ target molecules can ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450116666141219120125
更新日期:2015-01-01 00:00:00
abstract::Cyclooxygenase-2 (Cox-2) is an inducible enzyme involved in the conversion of arachidonic acid to prostaglandin and other eicosanoids. Molecular pathology studies have revealed that Cox-2 is over-expressed in cancer and stroma cells during tumor progression, and anti-cancer chemo-radiotherapies induce expression of Co...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945011795677764
更新日期:2011-06-01 00:00:00
abstract:OBJECTIVE:To investigated the use of mixed treatment comparison (MTC) meta-analysis models to summarize results from randomized clinical trials (RCTs) on approved pharmacological treatments for neovascular age-related macular degeneration (AMD). METHODS:The number of patients with visual loss or visual gain of 3 or mo...
journal_title:Current drug targets
pub_type: 杂志文章,meta分析,评审
doi:10.2174/138945011794182665
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abstract::At one time, atherosclerosis was thought to be a simple lipid storage disease. However, it is now recognized as a chronic and progressive inflammation of the arterial wall. Gene deletion experiments in murine models of atherosclerosis that reduce the inflammatory process also reduce disease severity. Identifying the i...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945007783220605
更新日期:2007-12-01 00:00:00
abstract::An understanding of the historical paths that have lead to our current state of knowledge in the field of platelet studies can be both illuminating and inspiring. Considering that the existence and function of platelets were initially described just barely over 100 years ago it is exciting to recognize how far our kno...
journal_title:Current drug targets
pub_type: 历史文章,杂志文章
doi:10.2174/138945011797635858
更新日期:2011-11-01 00:00:00
abstract::The sialyltransferase family represents a group of enzymes that transfers sialic acid from its common nucleotide sugar donor, CMP-NeuAc, to the terminal carbohydrates group of various glycoproteins and glycolipids. Cloning of these enzymes from mammalian sources indicated these are all type II membrane proteins with t...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945009788488422
更新日期:2009-06-01 00:00:00
abstract::Recently, a significant number of breast cancer (BC) patients have been diagnosed at an early stage. It is therefore critical to accurately predict the risk of recurrence and distant metastasis for better management of BC in this setting. Clinicopathologic patterns, particularly lymph node status, tumor size, and horm...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450121666200312105908
更新日期:2020-01-01 00:00:00
abstract::Programmed cell death, commonly associated with the term apoptosis, is an integrated intracellular program that plays a critical role in lymphoid tissue homeostasis. Alterations in this highly regulated process is a common feature of most lymphoid malignancies, thus facilitating tumor escape from traditional chemother...
journal_title:Current drug targets
pub_type: 杂志文章,评审
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更新日期:2010-07-01 00:00:00
abstract::Thromboembolic diseases such as deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI) and ischemic strokes are mainly responsible for people's morbidity and mortality and have severely affected the people's quality of life all over the world. According to WHO statistics, an average of 17 mill...
journal_title:Current drug targets
pub_type: 杂志文章,评审
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更新日期:2015-01-01 00:00:00
abstract::Stroke is one of the major causes of mortality and disability in adults in industrialized countries. Despite numerous preclinical studies and clinical trials in the field of cerebral ischemia, no pharmacological agent has been validated in the treatment of acute ischemic, except thrombolysis. Cerebral ischemia is not ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450111314070005
更新日期:2013-06-01 00:00:00
abstract::As early as 1940, Abraham and Chain described "an enzyme able to destroy penicillin". In the late 1940's, penicillin-resistant strains of Staphylococcus aureus were found to be a clinical problem. They produced a penicillinase that could hydrolyze the amide bond in the β-lactam ring. Later, an enzyme mediated by an R-...
journal_title:Current drug targets
pub_type: 历史文章,杂志文章,评审
doi:10.2174/1389450116666151001112859
更新日期:2016-01-01 00:00:00
abstract::It is well documented that elevated levels of PAI-1 in plasma can decrease the fibrinolytic activity in blood with an associated increased risk of thrombus formation. A diverse range of molecules including bacterial lipopolysaccharide (LPS), the inflammatory mediators tumor necrosis factor alpha (TNFalpha) and interle...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945007781662382
更新日期:2007-09-01 00:00:00