Abstract：
:Alzheimer's disease (AD) is a slow-progressing disease of the brain characterized by symptoms such as impairment of memory and other cognitive functions. AD is associated with an inflammatory process that involves astrocytes and microglial cells, among other components. Astrocytes are the most abundant type of glial cells in the central nervous system (CNS). They are involved in inducing neuroinflammation. The present study uses astrocyte-neuron cocultures to investigate how ARN14494, a serine palmitoyltransferase (SPT) inhibitor, affects the CNS in terms of anti-inflammation and neuroprotection. SPT is the first rate-limiting enzyme in the de novo ceramide synthesis pathway. Consistent evidence suggests that ceramide is increased in AD brain patients. After β-amyloid 1-42 injury in an in vitro model of AD, ARN14494 inhibits SPT activity and the synthesis of long-chain ceramides and dihydroceramides that are involved in AD progression. In mouse primary cortical astrocytes, ARN14494 prevents the synthesis of proinflammatory cytokines TNFα and IL1β, growth factor TGFβ1, and oxidative stress-related enzymes iNOS and COX2. ARN14494 also exerts neuroprotective properties in primary cortical neurons. ARN14494 decreases neuronal death and caspase-3 activation in neurons, when the neuroinflammation is attenuated in astrocytes. These findings suggest that ARN14494 protects neurons from β-amyloid 1-42 induced neurotoxicity through a variety of mechanisms, including antioxidation, antiapoptosis, and anti-inflammation. SPT inhibition could therefore be a safe therapeutic strategy for ameliorating the pathology of Alzheimer's disease.
journal_name
ACS Chem Neuroscijournal_title
ACS chemical neuroscienceauthors
De Vita T,Albani C,Realini N,Migliore M,Basit A,Ottonello G,Cavalli Adoi
10.1021/acschemneuro.8b00556subject
Has Abstractpub_date
2019-03-20 00:00:00pages
1627-1635issue
3issn
1948-7193journal_volume
10pub_type
杂志文章abstract：:Peripheral immunity is thought to be dysregulated in Parkinson's disease (PD) and may provide an avenue for novel immunotherapeutic interventions. Gut microbiota is a potential factor for modulating immunotherapy response. Considering the possibly complex role of the gut-brain axis in PD, we used a preclinical model t...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00386
更新日期：2020-10-21 00:00:00
abstract：:Tau aggregation in neuronal cells has recently received significant attention as a robust predictor of the progression of Alzheimer's disease (AD) because of its proven correlation with the degree of cognitive impairment in AD patients. Accordingly, noninvasive imaging of tau aggregates has been highlighted as a promi...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00224
更新日期：2017-10-18 00:00:00
abstract：:Quaternary ammonium analogues of atropine that are unable to cross the blood-brain barrier are used to alleviate peripheral muscarinic toxicity in animal models of epilepsy produced by systemic administration of pilocarpine or diisopropylfluorophosphate (DFP). Currently, methylatropine is the most popular and potent o...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.6b00334
更新日期：2017-04-19 00:00:00
abstract：:Oligomers of amyloid-β (AβO) are deemed key in synaptotoxicity and amyloid seeding of Alzheimer's disease (AD). However, the heterogeneous and dynamic nature of AβO and inadequate markers for AβO subtypes have stymied effective AβO identification and therapeutic targeting in vivo. We identified an AβO-subclass epitope...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00469
更新日期：2018-07-18 00:00:00
abstract：:The blood-brain barrier (BBB) is an important barrier that separates brain tissue from peripheral blood. The permeability of the BBB can be destroyed by external harmful factors, such as lipopolysaccharide (LPS), which contributes to neuroinflammation and central nervous system diseases. The present study aims to inve...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00537
更新日期：2020-12-16 00:00:00
abstract：:We propose a tripartite biochemical mechanism for memory. Three physiologic components are involved, namely, the neuron (individual and circuit), the surrounding neural extracellular matrix, and the various trace metals distributed within the matrix. The binding of a metal cation affects a corresponding nanostructure ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn300097b
更新日期：2012-08-15 00:00:00
abstract：:Essential hypertension is a major risk factor for cardiovascular disease that can lead eventually to structural and functional alterations in the brain. Accumulating evidence has suggested that the increased activities in renin-angiotensin system and sympathetic nerve participated in the pathogenesis of hypertension t...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.9b00699
更新日期：2020-06-03 00:00:00
abstract：:While fibrillar deposits of hyperphosphorylated protein tau are a key hallmark of several neurodegenerative diseases such as Alzheimer's disease, small oligomers have been speculated to be the key toxic aggregate species. Trivalent metal ions were shown to promote tau oligomer formation in vitro. However, little is kn...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.9b00459
更新日期：2020-03-18 00:00:00
abstract：:Neurons choose growth pathways with half hearted reluctance, behavior that may be appropriate to maintain fixed long lasting connections but not to regenerate them. We now recognize that intrinsic brakes on regrowth are widely expressed in these hesitant neurons and include classical tumor suppressor molecules. Here, ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章,评审
doi：10.1021/cn500110p
更新日期：2014-08-20 00:00:00
abstract：:Promotion of neurite outgrowth and synapse formation is a key step for nervous tissue regeneration. It is important for finding a new biomaterial to guide neuron growth to target neurons. Aminated graphene oxide (NH2-GO) displays electrical properties and dispersibility, which may change the surface charge of neurons ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.9b00625
更新日期：2020-02-19 00:00:00
abstract：:Angiotensin converting enzyme (ACE) is a dipeptidyl peptidase transmembrane bound enzyme. Generally, ACE inhibitors are used for the cardiovascular disorders. ACE inhibitors are primary agents for the management of hypertension, so these cannot be avoided for further use. The present Review focuses on the implications...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章,评审
doi：10.1021/cn500363g
更新日期：2015-04-15 00:00:00
abstract：:A hallmark of Alzheimer's disease (AD) is the formation of senile plaques comprised of the β-amyloid (Aβ) peptide. Aβ fibrillization is a complex nucleation-dependent process involving a variety of metastable intermediate aggregates and features the formation of inter- and intramolecular salt bridges involving lysine ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.9b00483
更新日期：2020-01-15 00:00:00
abstract：:Imidazo[2,1-b]benzothiazoles (IBTs) are a promising novel class of amyloid positron emission tomography (PET) radiopharmaceuticals for diagnosis of neurodegenerative disorders like Alzheimer's disease (AD). Their good in vivo imaging properties have previously been shown in preclinical studies. Among IBTs, fluorinated...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn5001827
更新日期：2015-03-18 00:00:00
abstract：:In vivo fast-scan cyclic voltammetry provides high-fidelity recordings of electrically evoked dopamine release in the rat striatum. The evoked responses are suitable targets for numerical modeling because the frequency and duration of the stimulus are exactly known. Responses recorded in the dorsal and ventral striatu...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章,评审
doi：10.1021/cn5000666
更新日期：2014-09-17 00:00:00
abstract：:The glycine receptor (GlyR) is a ligand-activated chloride channel, whose mutations are the major cause of hereditary hyperekplexia. The hyperekplexia-causing R271Q mutation, which is located at the extracellular outer mouth of the channel pore, dramatically impairs the GlyR function manifesting a reduced sensitivity ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00522
更新日期：2020-10-21 00:00:00
abstract：:Aggregation of hyperphosphorylated tau is the hallmark of several tauopathies, including Alzheimer's disease (AD). Although the mechanism underlying tau-associated neuronal damage remains unclear, it is believed that tau hyperphosphorylation is one of the key features in disease progression. A recent study demonstrate...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章,评审
doi：10.1021/acschemneuro.8b00632
更新日期：2019-01-16 00:00:00
abstract：:Myasthenia gravis (MG) is an autoimmune T cell-dependent B cell-mediated disorder of the neuromuscular junction (NMJ) characterized by fluctuating skeletal muscle weakness, most commonly attributed to pathogenic autoantibodies against postsynaptic nicotinic acetylcholine receptors (AChRs). Although MG pathogenesis is ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.9b00678
更新日期：2020-03-04 00:00:00
abstract：:A new generation of ligands designed to interact with the α-helix/β-strand discordant region of the amyloid-β peptide (Aβ) and to counteract its oligomerization is presented. These ligands are designed to interact with and stabilize the Aβ central helix (residues 13-26) in an α-helical conformation with increased inte...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.8b00485
更新日期：2019-03-20 00:00:00
abstract：:Online electrochemical detection techniques are the state-of-the-art for evaluating chemical communication in the brain underlying motivated behavior and decision making. In this Viewpoint, we discuss avenues for future technological development, as well as the requirement for increasingly sophisticated and interdisci...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章,评审
doi：10.1021/cn500322y
更新日期：2015-01-21 00:00:00
abstract：:The amyloid beta (Aβ) fibrillar aggregate is the hallmark of Alzheimer's disease (AD). Disassembling preformed fibril or inhibiting Aβ aggregation is considered as a therapeutic strategy for AD. Increasing evidence shows that green tea extracts, epigallocatechin-3-gallate (EGCG, containing an extra gallic acid ester g...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00277
更新日期：2020-06-17 00:00:00
abstract：:Central norepinephrine (NE) and dopamine (DA) are involved in a variety of physiological functions and behaviors. Accumulating evidence suggests that NE neurons originating from the locus coeruleus (LC) innervate DA neurons of the ventral tegmental area (VTA) and influence VTA-DA neural activity. However, the underlyi...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00078
更新日期：2017-09-20 00:00:00
abstract：:Amyloid-beta (Aβ) peptide misfolds into fibrillary aggregates (β-sheet) and is deposited as amyloid plaques in the cellular environment, which severely damages intraneuronal connections leading to Alzheimer's disease (AD) pathogenesis. Furthermore, neurons are rich in tubulin/microtubules, and the intracellular networ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.9b00115
更新日期：2019-05-15 00:00:00
abstract：:Although there is no reported genetic predisposition in contracting coronavirus disease 2019 (COVID-19), the mortality rate varies among different ethnic groups. Here we determined potential correlation between COVID-19 and spice consumption. The data from 163 countries including total cases, total deaths, and total r...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00239
更新日期：2020-06-17 00:00:00
abstract：:The pathogenesis of Parkinson's disease (PD) is multifactorial event. Combination therapies might be more effective in controlling the disease. Thus, the studies reported were designed to test the hypothesis that gastrodin (GAS)-induced de novo synthesis of nuclear factor E2-related factor 2 (Nrf2) and isorhynchophyll...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00247
更新日期：2018-03-21 00:00:00
abstract：:Aβ peptides, the main protein components of Alzheimer's disease (AD) plaques, derive from a proteolytic cleavage of the amyloid precursor protein. Due to heterogeneous cleavage sites, a series of Aβ peptides, including the major and widely studied species Aβ1-40 (Aβ40) and Aβ1-42 (Aβ42), are produced. In addition to t...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.6b00456
更新日期：2017-04-19 00:00:00
abstract：:Exploration of dendrimers for effective drug delivery is giving promising results. The present study was designed and performed to explore the dendrimeric (polyamidoamine-lactoferrin; PAMAM-Lf) formulations for the effective rivastigmine (RIV) delivery against the Alzheimer's induced animal model using lactoferrin as ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.9b00286
更新日期：2019-08-21 00:00:00
abstract：:Brain-eating amoebae (Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri) can cause opportunistic infections involving the central nervous system. It is troubling that the mortality rate is more than 90% despite advances in antimicrobial chemotherapy over the last few decades. Here, we describe urgent k...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00343
更新日期：2017-11-15 00:00:00
abstract：:We propose a tripartite mechanism to describe the processing of cognitive information (cog-info), comprising the (1) neuron, (2) surrounding neural extracellular matrix (nECM), and (3) numerous "trace" metals distributed therein. The neuron is encased in a polyanionic nECM lattice doped with metals (>10), wherein it p...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章,评审
doi：10.1021/cn300237r
更新日期：2013-06-19 00:00:00
abstract：:Proton magnetic spectroscopy (1H-MRS) is a noninvasive imaging technique that allows for the quantification of neurometabolic compounds at millimolar concentrations in the living human brain. This technique has been most often used to assess long-term changes in human brain metabolism in psychiatric disorders, pharmac...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00474
更新日期：2020-09-02 00:00:00
abstract：:The antioxidant activity of selenium, which is mainly conferred by its incorporation into dedicated selenoproteins, has been suggested as a possible neuroprotective approach for mitigating neuronal loss in Alzheimer's disease. However, there is inconsistent information with respect to selenium levels in the Alzheimer'...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00014
更新日期：2017-07-19 00:00:00
