Abstract:
:In aged subjects, late-onset Alzheimer's disease (LOAD) starts in the lateral entorhinal allocortex where a failure of clearance mechanisms triggers an accumulation of neurotoxic amyloid-β42 oligomers (Aβ42-os). In neurons and astrocytes, Aβ42-os enhance the transcription of Aβ precursor protein (APP) and β-secretase/BACE1 genes. Thus, by acting together with γ-secretase, the surpluses of APP and BACE1 amplify the endogenous production of Aβ42-os which pile up, damage mitochondria, and are oversecreted. At the plasmalemma, exogenous Aβ42-os bind neurons' and astrocytes' calcium-sensing receptors (CaSRs) activating a set of intracellular signaling pathways which upkeep Aβ42-os intracellular accumulation and oversecretion by hindering Aβ42-os proteolysis. In addition, Aβ42-os accumulating in the extracellular milieu spread and reach mounting numbers of adjacent and remoter teams of neurons and astrocytes which in turn are recruited, again via Aβ42-os•CaSR-governed mechanisms, to produce and release additional Aβ42-os amounts. This relentless self-sustaining mechanism drives AD progression toward upper cortical areas. Later on accumulating Aβ42-os elicit the advent of hyperphosphorylated (p)-Tau oligomers which acting together with Aβ42-os and other glial neurotoxins cooperatively destroy wider and wider cognition-related cortical areas. In parallel, Aβ42-os•CaSR signals also elicit an excess production and secretion of nitric oxide and vascular endothelial growth factor-A from astrocytes, of Aβ42-os and myelin basic protein from oligodendrocytes, and of proinflammatory cytokines, nitric oxide and (likely) Aβ42-os from microglia. Activated astrocytes and microglia survive the toxic onslaught, whereas neurons and oligodendrocytes increasingly die. However, we have shown that highly selective allosteric CaSR antagonists (calcilytics), like NPS 2143 and NPS 89626, efficiently suppress all the neurotoxic effects Aβ42-os•CaSR signaling drives in cultured cortical untransformed human neurons and astrocytes. In fact, calcilytics increase Aβ42 proteolysis and discontinue the oversecretion of Aβ42-os, nitric oxide, and vascular endothelial growth factor-A from both astrocytes and neurons. Seemingly, calcilytics would also benefit the other types of glial cells and cerebrovascular cells otherwise damaged by the effects of Aβ42-os•CaSR signaling. Thus, given at amnestic minor cognitive impairment (aMCI) or initial symptomatic stages, calcilytics could prevent or terminate the propagation of LOAD neuropathology and preserve human neurons' viability and hence patients' cognitive abilities.
journal_name
Front Physioljournal_title
Frontiers in physiologyauthors
Chiarini A,Armato U,Liu D,Dal Prà Idoi
10.3389/fphys.2016.00134subject
Has Abstractpub_date
2016-04-26 00:00:00pages
134issn
1664-042Xjournal_volume
7pub_type
杂志文章,评审abstract::Although interest in several areas of cephalopod research has emerged over the last decades (e.g., neurobiology, aquaculture, genetics, and welfare), especially following their 2010 inclusion in the EU Directive on the use of animals for experimental purposes, knowledge regarding the parasites of cephalopods is lackin...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.01573
更新日期:2018-11-20 00:00:00
abstract::For many hereditary disorders, although the underlying genetic mutation may be known, the molecular mechanism leading to hemolytic anemia is still unclear and needs further investigation. Previous studies revealed an increased intracellular Ca2+ in red blood cells (RBCs) from patients with sickle cell disease, thalass...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2017.00673
更新日期:2017-09-06 00:00:00
abstract::Atherosclerosis is considered as a chronic disease of arterial wall, with a strong contribution of inflammation. Dendritic cells (DCs) play a crucial role in the initiation of proatherogenic inflammatory response. Mature DCs present self-antigens thereby supporting differentiation of naïve T cells to effector cells th...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2014.00196
更新日期:2014-05-27 00:00:00
abstract::Octopamine (OA) is a prominent neuromodulator of invertebrate nervous systems, influencing multiple physiological processes. Among its many roles in insects are the initiation and maintenance of various rhythmic behaviors. Here, the neuromodulatory effects of OA on the components of the locust stomatogastric nervous s...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2012.00288
更新日期:2012-07-20 00:00:00
abstract::Yeast-like symbiotes (YLS), harbored in the abdomen fat-body cells of the rice brown planthopper (BPH), Nilaparvata lugens Stål (Hemiptera: Delphacidae), are vital to the growth and reproduction of their host. It is feasible to manipulate BPH infestation on rice by inhibiting YLS using fungicide. In this study, the fu...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2019.00089
更新日期:2019-02-11 00:00:00
abstract:Objective:Develop an automated approach to detect flash (<1.0 s) or prolonged (>2.0 s) capillary refill time (CRT) that correlates with clinician judgment by applying several supervised machine learning (ML) techniques to pulse oximeter plethysmography data. Materials and Methods:Data was collected in the Pediatric In...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.564589
更新日期:2020-10-06 00:00:00
abstract::Consumption of acidic foods and drinks and other factors that cause enamel wear are responsible for the daily enamel loss and degradation. Use of some toothpastes that have been showed to possess different properties of remineralisation and/or repair of the enamel surface may help to protect tooth enamel. The aim of t...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2014.00333
更新日期:2014-09-05 00:00:00
abstract::Perfluorooctanoic acid (PFOA) has been detected in various water bodies and caused harm to aquatic organisms. The aim of this study was to investigate the cytotoxicity and mechanism associated with autophagy and oxidative stress after exposure to PFOA (0, 1, 10, 100 μg/L) for 12 h on lymphocytes, which was isolated fr...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.01748
更新日期:2018-12-05 00:00:00
abstract::In addition to its roles in the maintenance of interstitial fluid homeostasis and immunosurveillance, the lymphatic system has a critical role in regulating transport of dietary lipids to the blood circulation. Recent work within the past two decades has identified an important relationship between lymphatic dysfuncti...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2020.00404
更新日期:2020-05-05 00:00:00
abstract::Background: The modulation of arachidonic acid (AA) metabolism pathway is identified in metabolic alterations after hypoxia exposure, but its biological function is controversial. We aimed at integrating plasma metabolomic and transcriptomic approaches to systematically explore the roles of the AA metabolism pathway i...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.00236
更新日期:2018-03-16 00:00:00
abstract::Coronary microembolization (CME) is an important clinical problem, and it is related to poor outcome. The specific molecular mechanisms of CME are not fully understood. In the present study, we established a mice model of CME. Isobaric tags for relative and absolute quantitation (iTRAQ) and liquid chromatography coupl...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.01318
更新日期:2018-09-19 00:00:00
abstract::Objective: Ventricular remodeling is considered the basis of heart failure and is involved in myocardial fibrosis. This study aimed to assess perindopril and a galectin-3 inhibitor (modified citrus pectin, MCP) for their effects on ventricular remodeling and myocardial fibrosis in rabbits with ischemic heart failure. ...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2019.00267
更新日期:2019-03-22 00:00:00
abstract::The underlying mechanisms in the development of diabetic nephropathy are currently unclear and likely consist of a series of dynamic events from the early to late stages of the disease. Diabetic nephropathy is currently without curative treatments and it is acknowledged that even the earliest clinical manifestation of...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2017.00211
更新日期:2017-04-11 00:00:00
abstract::Background: Whole-body electromyostimulation (WB-EMS) gained increasing interest in sports within recent years. However, few intervention studies have examined the effects of WB-EMS on trained subjects in comparison to conventional strength training. Objective: The aim of the present mini-meta-analysis of 5 recently c...
journal_title:Frontiers in physiology
pub_type:
doi:10.3389/fphys.2019.01336
更新日期:2019-11-08 00:00:00
abstract::Overconsumption of fructose leads to metabolic syndrome as a result of hypertension, insulin resistance, and hyperlipidemia. In this study, the renal function of animals submitted to high fructose intake was analyzed from weaning to adulthood using in vivo and ex vivo methods, being compared with a normal control grou...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.01433
更新日期:2018-10-10 00:00:00
abstract::Carbonic anhydrase II (CAII) is expressed along the nephron where it interacts with a number of transport proteins augmenting their activity. Aquaporin-1 (AQP1) interacts with CAII to increase water flux through the water channel. Both CAII and aquaporin-1 are expressed in the thin descending limb (TDL); however, the ...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2017.01108
更新日期:2018-01-05 00:00:00
abstract::Many disease fighting strategies have focused on the generation of NK cells, since they constitute the main immune barrier against cancer and intracellular pathogens such as viruses. Therefore, a predictive model for the development of NK cells would constitute a useful tool to test several hypotheses regarding the pr...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.01029
更新日期:2018-08-02 00:00:00
abstract::Acute kidney injury (AKI), which involves the loss of kidney function caused by damage to renal tubular cells, is an important public health concern. We previously showed that sirtuin (SIRT)3 protects the kidneys against mitochondrial damage by inhibiting the nucleotide-binding domain (NOD)-like receptor protein 3 (NL...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.01526
更新日期:2018-11-14 00:00:00
abstract::It is known that circulating angiotensin II (ANG-II) acts on the circumventricular organs (CVOs), which partially lack a normal blood-brain barrier, to stimulate pressor responses, vasopressin (AVP), and oxytocin (OT) secretion, as well as sodium and water intake. Although ANG-II type 1 receptors (AT1R) are expressed ...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.00430
更新日期:2018-05-01 00:00:00
abstract:UNLABELLED:Oxycodone (OXY) is one of the most commonly abused opiates during pregnancy. Perinatal opiate exposure (POE) is associated with neurobehavioral and hormone changes. Little is known about the effects of perinatal OXY on the cardiovascular (CV) responses to stress. OBJECTIVES:to determine the effects of POE o...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2013.00085
更新日期:2013-04-24 00:00:00
abstract::Currently, neuropathic pain is an underestimated socioeconomic health problem affecting millions of people worldwide, which incidence may increase in the next years due to chronification of several diseases, such as cancer and diabetes. Growing evidence links neuropathic pain present in several disorders [i.e., spinal...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2018.00095
更新日期:2018-02-14 00:00:00
abstract::As clinicians attempt to understand the underlying reasons for the vulnerability of different regions of the developing brain to injury, it is apparent that little is known as to how hypoxia-ischemia may affect the cerebrovasculature in the developing infant. Most of the research investigating the pathogenesis of peri...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2012.00424
更新日期:2012-11-09 00:00:00
abstract::The mitochondrial oxidative stress theory of aging posits that membrane susceptibility to peroxidation and the organization of the electron transport system (ETS) linked with reactive oxygen species (ROS) generation are two main drivers of lifespan. While a clear correlation has been established from species comparati...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2019.00946
更新日期:2019-07-26 00:00:00
abstract::Gene-targeted deletion of the potassium channel Kv1.3 (Kv1.3(-∕-)) results in "Super-smeller" mice with a sensory phenotype that includes an increased olfactory ability linked to changes in olfactory circuitry, increased abundance of olfactory cilia, and increased expression of odorant receptors and the G-protein, Gol...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2016.00178
更新日期:2016-05-19 00:00:00
abstract::Pinocembrin (PIN) is a natural flavonoid widely found in bee propolis with potent gastrointestinal protective effects. In consequence, PIN has great potential in preventing inflammatory bowel diseases (IBDs) while scant information is available. In this study, a dextran sulfate sodium (DSS)-induced rats ulcerative col...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2019.00908
更新日期:2019-07-19 00:00:00
abstract::Rapamycin, also known as sirolimus, is an antifungal agent and immunosuppressant drug used to prevent organ rejection in transplantation. However, little is known about the role of rapamycin in cardiac hypertrophy and the signaling pathways involved. Here, the effect of rapamycin was examined using phenylephrine (PE) ...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2016.00104
更新日期:2016-03-18 00:00:00
abstract::Glutathione (GSH) deficits have been observed in several mental or degenerative illness, and so has the metabolic syndrome. The impact of a decreased glucose metabolism on the GSH system is well-known, but the effect of decreased GSH levels on the energy metabolism is unclear. The aim of the present study was to inves...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2016.00142
更新日期:2016-04-21 00:00:00
abstract::The microbes in the gastrointestinal tract are separated from the host by a single layer of intestinal epithelial cells (IECs) that plays pivotal roles in maintaining homeostasis by absorbing nutrients and providing a physical and immunological barrier to potential pathogens. Preservation of homeostasis requires the c...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2019.01484
更新日期:2019-12-12 00:00:00
abstract::Several clinical studies have investigated the potential benefits of endothelin receptor antagonism in chronic pathologies such as diabetic kidney disease. However, fluid retention and edema have been identified as major side effects of endothelin receptor antagonists. In the present study we hypothesized that avosent...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2012.00103
更新日期:2012-04-18 00:00:00
abstract::Molar hypomineralisation (MH) is becoming globally recognised as a significant public health problem linked to childhood tooth decay. However, with causation and pathogenesis unclear after 100 years of investigation, better pathological understanding is needed if MH is to become preventable. Our studies have implicate...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.579015
更新日期:2020-09-30 00:00:00