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Pharmacology & Therapeutics

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https://www.readbyqxmd.com/read/30439458/synaptic-dysfunction-in-alzheimer-s-disease-mechanisms-and-therapeutic-strategies
#1
REVIEW
Yu Chen, Amy K Y Fu, Nancy Y Ip
Alzheimer's disease (AD), the most prevalent neurodegenerative disease in the elderly population, is characterized by progressive cognitive decline and pathological hallmarks of amyloid plaques and neurofibrillary tangles. However, its pathophysiological mechanisms are poorly understood, and diagnostic tools and interventions are limited. Here, we review recent research on the amyloid hypothesis and beta-amyloid-induced dysfunction of neuronal synapses through distinct cell surface receptors. We also review how tau protein leads to synaptotoxicity through pathological modification, localization, and propagation...
November 12, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30439457/gut-brain-axis-and-addictive-disorders-a-review-with-focus-on-alcohol-and-drugs-of-abuse
#2
REVIEW
Elisabet Jerlhag
Due to the limited efficacy of existing medications for addictive disorders including alcohol use disorder (AUD), the need for additional medications is substantial. Potential new medications for addiction can be identified through investigation of the neurochemical substrates mediating the ability of drugs of abuse such as alcohol to activate the mesolimbic dopamine system. Interestingly, recent studies implicate neuropeptides of the gut-brain axis as modulators of reward and addiction processes. The present review therefore summarizes the current studies investigating the ability of the gut-brain peptides ghrelin, glucagon-like peptide-1 (GLP-1), amylin and neuromedin U (NMU) to modulate alcohol- and drug-related behaviors in rodents and humans...
November 12, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30439456/altered-cancer-metabolism-in-mechanisms-of-immunotherapy-resistance
#3
REVIEW
Rishab Ramapriyan, Mauricio da Silva Caetano, Hampartsoum B Barsoumian, Ana Carolina P Mafra, Erika Pereira Zambalde, Hari Menon, Efrosini Tsouko, James W Welsh, Maria Angelica Cortez
Many metabolic alterations, including the Warburg effect, occur in cancer cells that influence the tumor microenvironment, including switching to glycolysis from oxidative phosphorylation, using opportunistic modes of nutrient acquisition, and increasing lipid biosynthesis. The altered metabolic landscape of the tumor microenvironment can suppress the infiltration of immune cells and other functions of antitumor immunity through the production of immune-suppressive metabolites. Metabolic dysregulation in cancer cells further affects the expression of cell surface markers, which interferes with immune surveillance...
November 12, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30439455/targeting-epigenetics-and-non-coding-rnas-in-atherosclerosis-from-mechanisms-to-therapeutics
#4
REVIEW
Suowen Xu, Danielle Kamato, Peter J Little, Shinichi Nakagawa, Jaroslav Pelisek, Zheng Gen Jin
Atherosclerosis, the principal cause of cardiovascular death worldwide, is a pathological disease characterized by fibro-proliferation, chronic inflammation, lipid accumulation, and immune disorder in the vessel wall. As the atheromatous plaques develop into advanced stage, the vulnerable plaques are prone to rupture, which causes acute cardiovascular events, including ischemic stroke and myocardial infarction. Emerging evidence has suggested that atherosclerosis is also an epigenetic disease with the interplay of multiple epigenetic mechanisms...
November 12, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30439454/neuropeptide-receptors-as-potential-pharmacological-targets-for-obesity
#5
REVIEW
Beatriz T Meneguetti, Marlon H Cardoso, Camila F Acosta Ribeiro, Mário R Felício, Ingrid B Pinto, Nuno C Santos, Cristiano Marcelo E Carvalho, Octávio L Franco
Obesity is a chronic multifactorial disease, characterized by an excessive accumulation of adipose tissue. It is usually the result of excessive food intake and/or low energy expenditure. Obesity can be triggered by lifestyle, nutritional, genetic, environmental, hormonal and psychological factors. Several strategies are used to treat obesity, including dietary reeducation, with balanced food intake, increased physical exercise, in order to promote energy expenditure and to overcome the insufficiency in weight reduction by other strategies, and the administration of drugs to treat obesity...
November 12, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30419258/the-role-of-dna-methylation-in-epigenetics-of-aging
#6
REVIEW
Archana Unnikrishnan, Willard M Freeman, Jordan Jackson, Jonathan D Wren, Hunter Porter, Arlan Richardson
Recent research suggests that epigenetics, especially DNA methylation, plays a mechanistic role in aging. Epigenetic clocks, which measure changes in a few hundred specific CpG sites, can accurately predict chronological age in a variety of species, including humans. These clocks are currently the best biomarkers for predicting mortality in humans. Additionally, several studies have characterized the effects of aging across the methylome in a wide variety of tissues from humans and mice. A small fraction (~2%) of the CpG sites show age-related changes, either hypermethylation or hypomethylation with aging...
November 9, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30347215/targeting-mcl-1-and-other-bcl-2-family-member-proteins-in-cancer-therapy
#7
REVIEW
Ryuji Yamaguchi, Lydia Lartigue, Guy Perkins
Regulation of both the extrinsic and the mitochondria-dependent intrinsic apoptotic pathways plays a key role in the development of the hematopoietic system, for sustaining cell survival during generation of various cell types, in eliminating cells with dual identities such as CD4/CD8 double-positive cells (Hettmann, Didonato, Karin, & Leiden, 1999; Ogasawara, Suda, & Nagata, 1995), for sustaining cells during the rapid clonal expansion phase (Schirmer, Vallejo, Weyand, & Gronzy, 1998), as well as eliminating cells during the contraction phase (Yajima et al...
October 19, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30347214/p53-in-kidney-injury-and-repair-mechanism-and-therapeutic-potentials
#8
REVIEW
Chengyuan Tang, Zhengwei Ma, Jiefu Zhu, Zhiwen Liu, Yuxue Liu, Yu Liu, Juan Cai, Zheng Dong
Acute kidney injury (AKI) is a major kidney disease with poor clinical outcome. Besides its acute consequence of high mortality, AKI may also contribute significantly to the occurrence and progression of chronic kidney diseases (CKD). Accumulating evidence has demonstrated that maladaptive and incomplete kidney repair after AKI leads to the development of renal fibrosis and, ultimately, CKD. p53, a well-known tumor suppressor, plays a critical role in AKI and subsequent kidney repair through the regulation of various cell biologic processes, including apoptosis, cell cycle arrest, and autophagy...
October 19, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30347213/revisiting-the-role-of-dihydroorotate-dehydrogenase-as-a-therapeutic-target-for-cancer
#9
REVIEW
Joseph T Madak, Armand Bankhead, Christine R Cuthbertson, Hollis D Showalter, Nouri Neamati
Identified as a hallmark of cancer, metabolic reprogramming allows cancer cells to rapidly proliferate, resist chemotherapies, invade, metastasize, and survive a nutrient-deprived microenvironment. Rapidly growing cells depend on sufficient concentrations of nucleotides to sustain proliferation. One enzyme essential for the de novo biosynthesis of pyrimidine-based nucleotides is dihydroorotate dehydrogenase (DHODH), a known therapeutic target for multiple diseases. Brequinar, leflunomide, and teriflunomide, all of which are potent DHODH inhibitors, have been clinically evaluated but failed to receive FDA approval for the treatment of cancer...
October 19, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30347212/antifungal-drugs-new-insights-in-research-development
#10
REVIEW
André Moraes Nicola, Patrícia Albuquerque, Hugo Costa Paes, Larissa Fernandes, Fabricio F Costa, Erika Seki Kioshima, Ana Karina Rodrigues Abadio, Anamélia Lorenzetti Bocca, Maria Sueli Felipe
The need for better antifungal therapy is commonly accepted in view of the high mortality rates associated with systemic infections, the low number of available antifungal classes, their associated toxicity and the increasing number of infections caused by strains with natural or acquired resistance. The urgency to expand the range of therapeutic options for the treatment of fungal infections has led researchers in recent decades to seek alternative antifungal targets when compared to the conventional ones currently used...
October 19, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30347211/the-neuropsychopharmacology-of-cannabis-a-review-of-human-imaging-studies
#11
REVIEW
Michael A P Bloomfield, Chandni Hindocha, Sebastian F Green, Matthew B Wall, Rachel Lees, Katherine Petrilli, Harry Costello, M Olabisi Ogunbiyi, Matthijs G Bossong, Tom P Freeman
The laws governing cannabis are evolving worldwide and associated with changing patterns of use. The main psychoactive drug in cannabis is Δ9 -tetrahydrocannabinol (THC), a partial agonist at the endocannabinoid CB1 receptor. Acutely, cannabis and THC produce a range of effects on several neurocognitive and pharmacological systems. These include effects on executive, emotional, reward and memory processing via direct interactions with the endocannabinoid system and indirect effects on the glutamatergic, GABAergic and dopaminergic systems...
October 19, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30347210/the-sphingosine-kinase-1-sphingosine-1-phosphate-axis-in-cancer-potential-target-for-anticancer-therapy
#12
REVIEW
Xiangjin Zheng, Wan Li, Liwen Ren, Jinyi Liu, Xiaocong Pang, Xiuping Chen, De Kang, Jinhua Wang, Guanhua Du
Sphingolipid metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate (S1P), play many important roles in cellular activities. Ceramide and sphingosine inhibit cell proliferation and induce cell apoptosis while S1P has the opposite effect. Maintaining a metabolic balance of sphingolipids is essential for growth and development of cells. Sphingosine kinase (SPHK) is an important regulator for keeping this balance. It controls the level of S1P and plays important roles in proliferation, migration, and invasion of cancer cells and tumor angiogenesis...
October 19, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30347209/role-of-the-12-lipoxygenase-pathway-in-diabetes-pathogenesis-and-complications
#13
REVIEW
A D Dobrian, M A Morris, D A Taylor-Fishwick, T R Holman, Y Imai, R G Mirmira, J L Nadler
12-lipoxygenase (12-LOX) is one of several enzyme isoforms responsible for the metabolism of arachidonic acid and other poly-unsaturated fatty acids to both pro- and anti-inflammatory lipid mediators. Mounting evidence has shown that 12-LOX plays a critical role in the modulation of inflammation at multiple checkpoints during diabetes development. Due to this, interventions to limit pro-inflammatory 12-LOX metabolites either by isoform-specific 12-LOX inhibition, or by providing specific fatty acid substrates via dietary intervention, has the potential to significantly and positively impact health outcomes of patients living with both type 1 and type 2 diabetes...
October 19, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30347208/organic-anion-transporting-polypeptide-oatp-transporter-expression-localization-and-function-in-the-human-intestine
#14
REVIEW
Stefan Oswald
Intestinal transporter proteins, along with drug metabolizing enzymes, play a major role in the disposition of orally administered drugs, nutrients and xenobiotics. In this regard, efflux transporters such as ABCB1 and ABCG2 can limit oral bioavailability, while uptake carriers such as PEPT1 have the potential to facilitate intestinal absorption. In contrast to the extensive information on intestinal efflux pumps, detailed knowledge about the respective uptake carriers is rather limited. During the last decade, organic anion transporting polypeptide (OATP) transporters have been frequently discussed as clinically relevant uptake transporters for endogenous compounds as well as drugs...
October 19, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30321555/statins-adverse-reactions-oxidative-stress-and-metabolic-interactions
#15
REVIEW
Aimei Liu, Qinghua Wu, Jingchao Guo, Irma Ares, José-Luis Rodríguez, María-Rosa Martínez-Larrañaga, Zonghui Yuan, Arturo Anadón, Xu Wang, María-Aránzazu Martínez
Statins, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are currently the most effective lipid-lowering drugs, effectively reducing the plasma total cholesterol and low-density lipoprotein, while also decreasing three triacylglycerols and increasing plasma high-density lipoprotein to a certain extent. However, the excessive or long-term use of statins can cause in vitro cytotoxicity, in vivo liver injury, liver necrosis, kidney damage, and myopathy in both human beings and animals. Many studies indicate that oxidative stress is involved in the various toxicities associated with statins, and various antioxidants have been evaluated to investigate their protective roles against statin-induced liver, kidney, and muscle toxicities...
October 12, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30321554/non-vitamin-k-oral-anticoagulants-noac-and-the-risk-of-myocardial-infarction-differences-between-factor-iia-and-factor-xa-inhibition
#16
REVIEW
Amin Polzin, Lisa Dannenberg, Georg Wolff, Carolin Helten, Alina Achilles, Thomas Hohlfeld, Tobias Zeus, Malte Kelm, Steffen Massberg, Tobias Petzold
Guidelines already recommend non-vitamin K oral anticoagulants (NOAC) over vitamin-K antagonists (VKA) for stroke prevention in patients with atrial fibrillation. However, recommendations are lacking with respect to which NOAC to use. At the moment, NOACs may employ two different molecular mechanisms: Factor IIa inhibition (dabigatran) and factor Xa inhibition (apixaban, edoxaban, rivaroxaban). The focus of this review is to compare and contrast potential differences between factor IIa- and factor Xa inhibition with respect to risk of myocardial infarction and to detail underlying mechanisms...
October 12, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30291908/acetylcholine-signaling-system-in-progression-of-lung-cancers
#17
REVIEW
Jamie R Friedman, Stephen D Richbart, Justin C Merritt, Kathleen C Brown, Nicholas A Nolan, Austin T Akers, Jamie K Lau, Zachary R Robateau, Sarah L Miles, Piyali Dasgupta
The neurotransmitter acetylcholine (ACh) acts as an autocrine growth factor for human lung cancer. Several lines of evidence show that lung cancer cells express all of the proteins required for the uptake of choline (choline transporter 1, choline transporter-like proteins) synthesis of ACh (choline acetyltransferase, carnitine acetyltransferase), transport of ACh (vesicular acetylcholine transport, OCTs, OCTNs) and degradation of ACh (acetylcholinesterase, butyrylcholinesterase). The released ACh binds back to nicotinic (nAChRs) and muscarinic receptors on lung cancer cells to accelerate their proliferation, migration and invasion...
October 3, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30291907/fighting-against-depression-with-trek-1-blockers-past-and-future-a-focus-on-spadin
#18
REVIEW
Alaeddine Djillani, Mariel Pietri, Jean Mazella, Catherine Heurteaux, Marc Borsotto
Depression is a devastating mood disorder and a leading cause of disability worldwide. Depression affects approximately one in five individuals in the world and represents heavy economic and social burdens. The neurobiological mechanisms of depression are not fully understood, but evidence highlights the role of monoamine neurotransmitter balance. Several antidepressants (ADs) are marketed to treat depression and related mood disorders. However, despite their efficacy, they remain nonspecific and unsafe because they trigger serious adverse effects...
October 3, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30291906/endothelins-in-inflammatory-neurological-diseases
#19
REVIEW
Pedro D'Orléans-Juste, Oscar B Akide Ndunge, Louisane Desbiens, Herbert B Tanowitz, Mahalia S Desruisseaux
Endothelins were discovered more than thirty years ago as potent vasoactive compounds. Beyond their well-documented cardiovascular properties, however, the contributions of the endothelin pathway have been demonstrated in several neuroinflammatory processes and the peptides have been reported as clinically relevant biomarkers in neurodegenerative diseases. Several studies report that endothelin-1 significantly contributes to the progression of neuroinflammatory processes, particularly during infections in the central nervous system (CNS), and is associated with a loss of endothelial integrity at the blood brain barrier level...
October 3, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30268773/targeting-programmed-cell-death-1-pd-1-and-ligand-pd-l1-a-new-era-in-cancer-active-immunotherapy
#20
REVIEW
Anastasia Constantinidou, Constantinos Alifieris, Dimitrios T Trafalis
Improved understanding of the immune system and its role in cancer development and progression has led to impressive advances in the field of cancer immunotherapy over the last decade. Whilst the field is rapidly evolving and the list of drugs receiving regulatory approval for the treatment of various cancers is fast growing, the group of PD1- PDL-1 inhibitors is establishing a leading role amongst immunomodulatory agents. PD1- PDL-1 inhibitors act against pathways involved in adaptive immune suppression resulting in immune checkpoint blockade...
September 28, 2018: Pharmacology & Therapeutics
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