Abstract：
:In the last few years, exciting properties have emerged regarding the activation, signaling, mechanisms of action, and therapeutic targeting of the two types of neurotrophin receptors: the p75NTR with its intracellular and extracellular peptides, the Trks, their precursors and their complexes. This review summarizes these new developments, with particular focus on neurodegenerative diseases. Based on the evolving knowledge, innovative concepts have been formulated regarding the pathogenesis of these diseases, especially the Alzheimer's and two other, the Parkinson's and Huntington's diseases. The medical progresses include original procedures of diagnosis, started from studies in mice and now investigated for human application, based on innovative classes of receptor agonists and blockers. In parallel, comprehensive studies have been and are being carried out for the development of drugs. The relevance of these studies is based on the limitations of the therapies employed until recently, especially for the treatment of Alzheimer's patients. Starting from well known drugs, previously employed for non-neurodegenerative diseases, the ongoing progress has lead to the development of small molecules that cross rapidly the blood-brain barrier. Among these molecules the most promising are specific blockers of the p75NTR receptor. Additional drugs, that activate Trk receptors, were shown effective against synaptic loss and memory deficits. In the near future such approaches, coordinated with treatments with monoclonal antibodies and with developments in the microRNA field, are expected to improve the therapy of neurodegenerative diseases, and may be relevant also for other human disease conditions.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Meldolesi Jdoi
10.1016/j.phrs.2017.04.024subject
Has Abstractpub_date
2017-07-01 00:00:00pages
129-137eissn
1043-6618issn
1096-1186pii
S1043-6618(17)30484-Xjournal_volume
121pub_type
杂志文章,评审abstract：:The lack of availability of appropriate medicines for children is an extensive and well known problem. As a consequence off label or unlicensed administration of medicinal products in every day paediatric practice is frequent. A variety of obstacles hinder the development of paediatric indications for drugs primarily ...
journal_title：Pharmacological research
pub_type： 社论,评审
doi：10.1016/j.phrs.2011.01.016
更新日期：2011-09-01 00:00:00
abstract：:A bovine dopamine transporter (bDAT) cDNA was transfected into CV-1 cells, a cell line that lacks vesicular storage and release mechanisms. Using this cell line, the effects of neuroleptic drugs on DAT-mediated uptake and release of dopamine (DA) were examined. All of the neuroleptic drugs tested, inhibited DA uptakes...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：
更新日期：1997-05-01 00:00:00
abstract：:The gut microbiota and its short chain fatty acid (SCFA) metabolites have been established to play an important protective role against neurodegenerative diseases. Our previous study demonstrated that cerebral ischemic stroke triggers dysfunctional gut microbiota and increased intestinal permeability. In this study, w...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2019.104403
更新日期：2019-10-01 00:00:00
abstract：:A global transcriptional regulator, MgrA, was previously identified as a key determinant of virulence in Staphylococcus aureus. An 80% EtOH extract of Uncaria gambier was found to attenuate the virulence of S. aureus via its effects on MgrA. Using bioassay-guided fractionation, a polyphenolic polymer, uncariitannin, w...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2019.104328
更新日期：2019-09-01 00:00:00
abstract：:"Funny" (f) channels underlie the cardiac "pacemaker"I(f) current, originally described as an inward current activated on hyperpolarization to the diastolic range of voltages in sino-atrial node myocytes [Brown, HF, DiFrancesco, D, Noble, SJ. How does adrenaline accelerate the heart? Nature 1979;280:235-236]. The invo...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2006.03.006
更新日期：2006-05-01 00:00:00
abstract：:In the present study the effect of ketamine, a dissociative anaesthetic, on the GABA- and on the specific GABAA-agonist muscimol-induced responses of the isolated guinea pig ileum was investigated. GABA as well as muscimol produce a concentration-dependent contractile effect on the duodenum, jejunum and ileum. The sen...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/1043-6618(95)80086-7
更新日期：1995-06-01 00:00:00
abstract：:Osteopontin (OPN) is known as an active player in the progression of vascular remodeling diseases, however, the precise role in the proliferation of vascular smooth muscle cells (VSMC) is unclear. Thus, this study investigated the role of OPN in VSMC proliferation induced by 4-hydroxynonenal (HNE), and identified the ...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2016.03.041
更新日期：2016-06-01 00:00:00
abstract：:The insulinotropic action of the meglitinide analogues KAD-1229, A-4166 and repaglinide was examined in rat pancreatic islets deprived of exogenous nutrient or incubated in the presence of nutrient secretagogues such as D-glucose and the methyl esters of pyruvic acid, succinic acid and glutamic acid. The meglitinide a...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1996.0026
更新日期：1996-03-01 00:00:00
abstract：:The transparent bodies of see-through medaka fish has led to their use as models for in vivo cell and tissue imaging. However, these fish may also prove useful as models for pathological processes. Accumulating reports show that pathology in fish is similar to that in mammals, including humans. In this study, patholog...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2008.09.011
更新日期：2008-11-01 00:00:00
abstract：:Exogenous hydrogen sulfide (H2S) protects against myocardial ischemia/reperfusion injury but the mechanism of action is unclear. The present study investigated the effect of GYY4137, a slow-releasing H2S donor, on myocardial infarction given specifically at reperfusion and the signalling pathway involved. Thiobutabarb...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2016.06.028
更新日期：2016-09-01 00:00:00
abstract：:In 1996, Dr. Costa was invited by Prof. Boris Astrachan, Chairman of the Department of Psychiatry at the University of Illinois at Chicago, to direct the research of the "Psychiatric Institute, Department of Psychiatry, School of Medicine, at the University of Illinois at Chicago." He was asked to develop a seminal re...
journal_title：Pharmacological research
pub_type： 历史文章,杂志文章,评审
doi：10.1016/j.phrs.2011.05.026
更新日期：2011-10-01 00:00:00
abstract：:The herbal formulation Sinpo-Tang (SPT) has long been used for various allergic diseases. We investigated the effect of SPT on the mast cell-mediated anaphylactic reactions in vivo and in vitro murine models. SPT dose dependently inhibited compound 48/80-induced ear swelling response and histamine release. SPT (0.001-...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043661802002037
更新日期：2002-11-01 00:00:00
abstract：:Bioequivalence studies are mainly required to demonstrate the interchangeability of multisource pharmaceutical products, usually called generics. A pivotal investigation projected and conducted in compliance with specific guidelines allows a replicative company to register a generic drug via an ANDA (abbreviated new d...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043-6618(05)80028-3
更新日期：1995-10-01 00:00:00
abstract：:Insulin-like growth factor-1, angiotensin-(1-7) and angiotensin-(1-9) have been proposed to be important mediators in cardioprotection. A large body of evidence indicates that insulin like growth factor-1 has pleotropic actions in the heart (i.e., contractility, metabolism, hypertrophy, autophagy, senescence and cell ...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2015.06.018
更新日期：2015-11-01 00:00:00
abstract：:The effect of chloroquine and other antimalarial drugs on glutamate dehydrogenase activity was studied in liver and renal mitochondria as well as in kidney-cortex tubules of rabbit. In permeabilized mitochondria, with free access of substrates and drugs to glutamate dehydrogenase, 100 microns chloroquine decreased bot...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1996.0108
更新日期：1997-01-01 00:00:00
abstract：:Flibanserin has been reported to be an agonist at 5-HT1A-receptors and an antagonist at 5-HT2A receptors, with higher affinity for 5-HT1A receptors. Despite the fact that less receptor occupation is required by full agonists than by antagonists to exert their effects, flibanserin was shown to exert 5-HT2A antagonism a...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.2000.0762
更新日期：2001-02-01 00:00:00
abstract：:Cardiac intracellular Na+and Ca2+homeostasis is regulated by the concerted action of ion channels, pumps and exchangers. The Na+, K+-ATPase produces the electrochemical concentration gradient for Na+, which is the driving force for Ca2+removal from the cytosol via the Na+/Ca2+exchange. Reduction of this gradient by in...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1006/phrs.1998.0416
更新日期：1999-03-01 00:00:00
abstract：:As an essential component of the innate immune system, Toll-like receptors (TLRs) are a family of well-recognized ligand-binding receptors found in various organisms and initiate host immune responses. Activation of TLRs signaling pathways lead to the induction of numerous genes that function in host defense. Baicalin...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2020.104890
更新日期：2020-08-01 00:00:00
abstract：:The principle of mechanopharmacology of airway smooth muscle (ASM) is based on the premise that physical agitation, such as pressure oscillation applied to an airway, is able to induce bronchodilation by reducing contractility and softening the cytoskeleton of ASM. Although the underlying mechanism is not entirely cle...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2020.104995
更新日期：2020-09-01 00:00:00
abstract：:The aminosteroid derivative RM-133 is an effective anticancer molecule for which proof of concept has been achieved in several mouse xenograph models (HL-60, MCF-7, PANC-1 and OVCAR-3). To promote this new family of molecules toward a clinical phase 1 trial, the mechanism of action governing the anticancer properties ...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2017.12.024
更新日期：2018-02-01 00:00:00
abstract：:We have recently synthesized a new series of 4,5-dihydrobenzo-oxa-cycloheptapyrazole derivatives with the aim to discover novel CB1 antagonist agents characterized by anti-obesity activity comparable to that of SR141716A but with reduced adverse effects such as anxiety and depression. Within the novel class, the CB1 a...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2013.06.001
更新日期：2013-08-01 00:00:00
abstract：:The EEG and behavioural changes induced by the administration of polyamines (spermine and spermidine) were studied in rabbit. Spermine and spermidine were administered at different doses (200 and 400 micrograms) into the mesencephalic ventricle (i.c.v.) both as a bolus and in constant perfusion (60 min duration). We a...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/1043-6618(90)90754-2
更新日期：1990-07-01 00:00:00
abstract：PURPOSE OF THE RESEARCH:Overexpression of the human dimethylarginine dimethylaminohydrolase type 1 (hDDAH1) gene was reported to have beneficial cardiovascular effects in mice. To date, it is unclear whether these effects are related to enhanced metabolic clearance of asymmetric dimethylarginine (ADMA) and l-N(G)-mono-...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2009.08.001
更新日期：2009-12-01 00:00:00
abstract：:The effect of the inhalation of vaporized ethanol on injected [1-14C]pyruvate kinetics was studied in mice. The [1-14C]pyruvate kinetics were modelled by means of a four-compartment closed model, i.e. injected site, blood, periphery and expired 14CO2. The results show that the inhalation of vaporized ethanol can stimu...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1997.0261
更新日期：1998-01-01 00:00:00
abstract：:The aqueous extract from aerial parts of Artemisia copa Phil. (Compositae), was evaluated for antinociceptive activity using writhing, formalin, and hot-plate tests in mice. A dose-related antinociceptive response was obtained in the writhing test at doses of 500 and 1000 mg/kg p.o. (percentage of inhibition 23.3 and ...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2003.12.016
更新日期：2004-07-01 00:00:00
abstract：:Cardiac arrhythmia can be a serious complication during general anaesthesia of patients suffering from cardiac arrhythmias and using antiarrhythmic drugs. The aim of the present experiments was to establish the way in which lidocaine and verapamil influence haemodynamic parameters of rabbits after midazolam anaesthesi...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1998.0464
更新日期：1999-06-01 00:00:00
abstract：:Adaptive responses to stress are critical to enhance physical and mental well-being, but excessive or prolonged stress may cause inadaptability and increase the risks of psychiatric disorders, such as depression. GABABR signaling is fundamental to brain function and has been identified in neuropsychiatric disorders. K...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2020.105355
更新日期：2021-01-01 00:00:00
abstract：:Psoriasis is one of the most common skin disorders characterized by erythematous plaques that result from hyperproliferative keratinocytes and infiltration of inflammatory leukocytes into dermis and epidermis. Recent studies suggest that IL-23/IL-17A/IL-22 cytokine axis plays an important role in the pathogenesis of p...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2015.06.001
更新日期：2015-09-01 00:00:00
abstract：:Several factors such as proteinuria and renal fibrosis may be important in the progression of many forms of chronic renal diseases. The purposes of the current study were to investigate the progressive renal failure of the rats with surgical renal mass reduction (RMR) and the effect of the angiotensin-converting enzym...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043-6618(02)00321-3
更新日期：2003-03-01 00:00:00
abstract：:Gossypol, a cottonseed extract, has been shown to have antiproliferative activity in a variety of cancer cell lines. The objective of this study was to determine the inhibitory effects of gossypol on cell proliferation. Five human carcinoma cell lines were evaluated including endometrial (RL95-2), ovarian (SKOV-3), me...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s104366180200230x
更新日期：2002-12-01 00:00:00
