journal
https://read.qxmd.com/read/38527459/comprehensive-assessment-of-ischemic-stroke-in-nonhuman-primates-neuroimaging-behavioral-and-serum-proteomic-analysis
#1
JOURNAL ARTICLE
Ge Li, Lan Lan, Tingting He, Zheng Tang, Shuhua Liu, Yunfeng Li, Zhongqiang Huang, Yalun Guan, Xuejiao Li, Yu Zhang, Hsin-Yi Lai
Ischemic strokes, prevalence and impactful, underscore the necessity of advanced research models closely resembling human physiology. Our study utilizes nonhuman primates (NHPs) to provide a detailed exploration of ischemic stroke, integrating neuroimaging data, behavioral outcomes, and serum proteomics to elucidate the complex interplay of factors involved in stroke pathophysiology. We observed a consistent pattern in infarct volume, peaking at 1-month postmiddle cerebral artery occlusion (MCAO) and then stabilized...
March 25, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38526238/targeted-neuroinflammation-mitigation-using-inflammasome-inhibiting-nanoligomers-is-therapeutic-in-an-experimental-autoimmune-encephalomyelitis-mouse-model
#2
JOURNAL ARTICLE
Sadhana Sharma, Sydney Risen, Vincenzo S Gilberto, Sean Boland, Anushree Chatterjee, Julie A Moreno, Prashant Nagpal
Multiple sclerosis (MS) is a debilitating autoimmune disease that impacts millions of patients worldwide, disproportionately impacting women (4:1), and often presenting at highly productive stages of life. This disease affects the spinal cord and brain and is characterized by severe neuroinflammation, demyelination, and subsequent neuronal damage, resulting in symptoms like loss of mobility. While untargeted and pan-immunosuppressive therapies have proven to be disease-modifying and manage (or prolong the time between) symptoms in many patients, a significant fraction are unable to achieve remission...
March 25, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38525994/substrate-selection-criteria-in-regulated-intramembrane-proteolysis
#3
REVIEW
Celine Moser, Nadja Guschtschin-Schmidt, Mara Silber, Julia Flum, Claudia Muhle-Goll
Alzheimer's disease is the most common form of dementia encountered in an aging population. Characteristic amyloid deposits of Aβ peptides in the brain are generated through cleavage of amyloid precursor protein (APP) by γ-secretase, an intramembrane protease. Cryo-EM structures of substrate γ-secretase complexes revealed details of the process, but how substrates are recognized and enter the catalytic site is still largely ignored. γ-Secretase cleaves a diverse range of substrate sequences without a common consensus sequence, but strikingly, single point mutations within the transmembrane domain (TMD) of specific substrates may greatly affect cleavage efficiencies...
March 25, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38525886/design-synthesis-and-biological-evaluation-of-ferulic-acid-template-based-novel-multifunctional-ligands-targeting-nlrp3-inflammasome-for-the-management-of-alzheimer-s-disease
#4
JOURNAL ARTICLE
Gourav Singh, Gauri Shankar, Samir Ranjan Panda, Sunil Kumar, Sanskriti Rai, Himanshu Verma, Prabhat Kumar, Prasanta Kumar Nayak, V G M Naidu, Saripella Srikrishna, Saroj Kumar, Gyan Modi
Alzheimer's disease (AD) is the most common cause of dementia, which arises due to low levels of acetyl and butyrylcholines, an increase in oxidative stress, inflammation, metal dyshomeostasis, Aβ and tau aggregations. The currently available drugs for AD treatment can provide only symptomatic relief without interfering with pathological hallmarks of the disease. In our ongoing efforts to develop naturally inspired novel multifunctional molecules for AD, systematic SAR studies on EJMC-4e were caried out to improve its multifunctional properties...
March 25, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38523263/thiophene-based-ligands-for-specific-assignment-of-distinct-a%C3%AE-pathologies-in-alzheimer-s-disease
#5
JOURNAL ARTICLE
Therése Klingstedt, Linda Lantz, Hamid Shirani, Junyue Ge, Jörg Hanrieder, Ruben Vidal, Bernardino Ghetti, K Peter R Nilsson
Aggregated species of amyloid-β (Aβ) are one of the pathological hallmarks in Alzheimer's disease (AD), and ligands that selectively target different Aβ deposits are of great interest. In this study, fluorescent thiophene-based ligands have been used to illustrate the features of different types of Aβ deposits found in AD brain tissue. A dual-staining protocol based on two ligands, HS-276 and LL-1, with different photophysical and binding properties, was developed and applied on brain tissue sections from patients affected by sporadic AD or familial AD associated with the PSEN1 A431E mutation...
March 24, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38511291/selective-potentiation-of-the-%C3%AE-4-3-%C3%AE-2-2-nicotinic-acetylcholine-receptor-response-by-ns9283-analogues
#6
JOURNAL ARTICLE
Rebecca Appiani, Franco Viscarra, Philip C Biggin, Isabel Bermudez, Alessandro Giraudo, Marco Pallavicini, Cristiano Bolchi
NS9283, 3-(3-pyridyl)-5-(3-cyanophenyl)-1,2,4-oxadiazole, is a selective positive allosteric modulator of (α4)3 (β2)2 nicotinic acetylcholine receptors (nAChRs). It has good subtype selective therapeutic potential afforded by its specific binding to the unique α4-α4 subunit interface present in the (α4)3 (β2)2 nAChR. However, there is currently a lack of structure activity relationship (SAR) studies aimed at developing a class of congeners endowed with the same profile of activity that can help consolidate the druggability of the α4-α4 subunit interface...
March 21, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38507813/targeting-neuroinflammation-by-pharmacologic-downregulation-of-inflammatory-pathways-is-neuroprotective-in-protein-misfolding-disorders
#7
JOURNAL ARTICLE
Sydney J Risen, Sean W Boland, Sadhana Sharma, Grace M Weisman, Payton M Shirley, Amanda S Latham, Arielle J D Hay, Vincenzo S Gilberto, Amelia D Hines, Stephen Brindley, Jared M Brown, Stephanie McGrath, Anushree Chatterjee, Prashant Nagpal, Julie A Moreno
Neuroinflammation plays a crucial role in the development of neurodegenerative protein misfolding disorders. This category of progressive diseases includes, but is not limited to, Alzheimer's disease, Parkinson's disease, and prion diseases. Shared pathogenesis involves the accumulation of misfolded proteins, chronic neuroinflammation, and synaptic dysfunction, ultimately leading to irreversible neuronal loss, measurable cognitive deficits, and death. Presently, there are few to no effective treatments to halt the advancement of neurodegenerative diseases...
March 20, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38507566/prenatal-fluoxetine-exposure-influences-glucocorticoid-receptor-mediated-activity-in-the-prefrontal-cortex-of-adolescent-rats-exposed-to-acute-stress
#8
JOURNAL ARTICLE
Maria Teresa Gallo, Beatrice Dolci, Fabio Fumagalli, Paola Brivio, Francesca Calabrese
Any deviation from the programmed processes of brain development may modify its formation and functions, thereby precipitating pathological conditions, which often become manifest in adulthood. Exposure to a challenge during crucial periods of vulnerability, such as adolescence, may reveal molecular changes preceding behavioral outcomes. Based on a previous study showing that prenatal fluoxetine (FLX) leads to the development of an anhedonic-like behavior in adult rats, we aimed to assess whether the same treatment regimen (i...
March 20, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38506562/identification-of-new-ketamine-metabolites-and-their-detailed-distribution-in-the-mammalian-brain
#9
JOURNAL ARTICLE
Theodosia Vallianatou, Carina de Souza Anselmo, Ioanna Tsiara, Nicholas B Bèchet, Iben Lundgaard, Daniel Globisch
Ketamine is a common anesthetic used in human and veterinary medicine. This drug has recently received increased medical and scientific attention due to its indications for neurological diseases. Despite being applied for decades, ketamine's entire metabolism and pharmacological profile have not been elucidated yet. Therefore, insights into the metabolism and brain distribution are important toward identification of neurological effects. Herein, we have investigated ketamine and its metabolites in the pig brain, cerebrospinal fluid, and plasma using mass spectrometric and metabolomics analysis...
March 20, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38506367/rapid-fret-assay-for-the-early-detection-of-alpha-synuclein-aggregation-in-parkinson-s-disease
#10
JOURNAL ARTICLE
Hang Yu, Rui Feng, Fenglin Chen, Zuodong Wu, Dehai Li, Xue Qiu
Alpha-synuclein (α-Syn) is a key protein of Parkinson's disease (PD). Oligomers formed by misfolding and aggregation of α-Syn can cause many pathological phenomena and aggravate the development of PD. Therefore, sensitive and accurate detection of oligomers is essential to understanding the pathology of PD and beneficial to screening and developing new drugs against PD. Here, we demonstrated a simple and sensitive method to detect the early aggregation of α-Syn via Förster resonance energy transfer (FRET) technology...
March 20, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38503425/effect-of-natural-osmolytes-on-recombinant-tau-monomer-propensity-of-oligomerization-and-aggregation
#11
JOURNAL ARTICLE
Sharif Arar, Md Anzarul Haque, Nemil Bhatt, Yingxin Zhao, Rakez Kayed
The pathological misfolding and aggregation of the microtubule associated protein tau (MAPT), a full length Tau2N4R with 441aa, is considered the principal disease relevant constituent in tauopathies including Alzheimer's disease (AD) with an imbalanced ratio in 3R/4R isoforms. The exact cellular fluid composition, properties, and changes that coincide with tau misfolding, seed formation, and propagation events remain obscure. The proteostasis network, along with the associated osmolytes, is responsible for maintaining the presence of tau in its native structure or dealing with misfolding...
March 19, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38501754/label-free-in-situ-chemical-characterization-of-amyloid-plaques-in-human-brain-tissues
#12
JOURNAL ARTICLE
James Everett, Jake Brooks, Vindy Tjendana Tjhin, Frederik Lermyte, Ian Hands-Portman, Germán Plascencia-Villa, George Perry, Peter J Sadler, Peter B O'Connor, Joanna F Collingwood, Neil D Telling
The accumulation of amyloid plaques and increased brain redox burdens are neuropathological hallmarks of Alzheimer's disease. Altered metabolism of essential biometals is another feature of Alzheimer's, with amyloid plaques representing sites of disturbed metal homeostasis. Despite these observations, metal-targeting disease treatments have not been therapeutically effective to date. A better understanding of amyloid plaque composition and the role of the metals associated with them is critical. To establish this knowledge, the ability to resolve chemical variations at nanometer length scales relevant to biology is essential...
March 19, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38501572/histone-lysine-demethylase-kdm5-inhibitor-cpi-455-induces-astrocytogenesis-in-neural-stem-cells
#13
JOURNAL ARTICLE
Thin Thin San, Junhyung Kim, Hyun-Jung Kim
Lysine-specific histone demethylase 5A (KDM5A) is known to facilitate proliferation in cancer cells and maintain stemness to repress the astrocytic differentiation of neural stem cells (NSCs). In the study presented here, we investigated the effect of a KDM5 inhibitor, CPI-455, on NSC fate control. CPI-455 induced astrocytogenesis in NSCs during differentiation. Kdm5a , but not Kdm5c , knockdown induced glial fibrillary acidic protein ( Gfap ) transcription. CPI-455 induced signal transducer and activator of transcription 3, increased bone morphogenetic protein 2 expression, and enhanced mothers against decapentaplegic homolog 1/5/9 phosphorylation...
March 19, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38499363/the-dynamics-of-resting-state-eeg-and-salivary-trace-elements-in-patients-with-obsessive-compulsive-disorder
#14
JOURNAL ARTICLE
Galina Portnova, Guzal M Khayrullina, Ivan V Mikheev, Sofiya M Byvsheva, Elena V Proskurnina, Olga Martynova
The study of salivary microelements and their neurophysiological and behavioral correlates in patients with obsessive-compulsive disorder (OCD) is a pressing issue in modern psychiatry, which, however, lacks adequate research at this time. In this study, we tested the dynamics of behavioral parameters, resting-state electroencephalogram (EEG), and salivary iron, copper, manganese, magnesium, and zinc in 30 healthy volunteers and 30 individuals with OCD before and after an emotional antisaccade task. The eye-movement data served as a measure of behavioral performance...
March 18, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38499042/serotonin-signaling-through-lipid-membranes
#15
REVIEW
Liubov S Kalinichenko, Johannes Kornhuber, Steffen Sinning, Jana Haase, Christian P Müller
Serotonin (5-HT) is a vital modulatory neurotransmitter responsible for regulating most behaviors in the brain. An inefficient 5-HT synaptic function is often linked to various mental disorders. Primarily, membrane proteins controlling the expression and activity of 5-HT synthesis, storage, release, receptor activation, and inactivation are critical to 5-HT signaling in synaptic and extra-synaptic sites. Moreover, these signals represent information transmission across membranes. Although the lipid membrane environment is often viewed as fairly stable, emerging research suggests significant functional lipid-protein interactions with many synaptic 5-HT proteins...
March 18, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38488720/investigating-a-novel-neurodegenerative-disease-toxic-mechanism-involving-lipid-binding-specificity-of-amyloid-oligomers
#16
JOURNAL ARTICLE
Sarah S Hirschbeck, Edward T Lindberg, Joshua H Jang, MaKenna R Jacob, Kristi L Lazar Cantrell, Thanh D Do
Exploring the mechanisms underlying the toxicity of amyloid oligomers (AOs) presents a significant opportunity for discovering cures and developing treatments for neurodegenerative diseases. Recently, using a combination of ion mobility spectrometry-mass spectrometry (IMS-MS) and X-ray crystallography (XRC), we showed that the peptide KVKVLWDVIEV, which is the G95W mutant of αB-Crystallin (90-100) and abbreviated as G6W, self-assembles up to a dodecamer that structurally resembles lipid transport proteins...
March 15, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38484276/research-report-a-link-between-sertraline-treatment-and-susceptibility-to-mis-information
#17
JOURNAL ARTICLE
Michal Piksa, Karolina Noworyta, Jan Piasecki, Aleksander Gundersen, Jonas Kunst, Mikolaj Morzy, Rafal Rygula
Recent research revealed that several psycho-cognitive processes, such as insensitivity to positive and negative feedback, cognitive rigidity, pessimistic judgment bias, and anxiety, are involved in susceptibility to fake news. All of these processes have been previously associated with depressive disorder and are sensitive to serotoninergic manipulations. In the current study, a link between chronic treatment with the selective serotonin reuptake inhibitor (SSRI) sertraline and susceptibility to true and fake news was examined...
March 14, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38483468/influence-of-cigarette-aerosol-in-alpha-synuclein-oligomerization-and-cell-viability-in-sh-sy5y-implications-for-parkinson-s-disease
#18
JOURNAL ARTICLE
Yu-Xin Shen, Pe-Shuen Lee, Ming-Chu Teng, Jhih-Hong Huang, Chia C Wang, Hsiu-Fang Fan
Although cigarette aerosol exposure is associated with various adverse health issues, its impact on Parkinson's disease (PD) remains elusive. Here, we investigated the effect of cigarette aerosol extract (CAE) on SH-SY5Y cells for the first time, both with and without α-synuclein (α-Syn) overexpression. We found that α-Syn aggravates CAE-induced cell death, oxidative stress, and mitochondrial dysfunction. Fluorescence cross-correlation spectroscopy (FCCS) revealed a dual distribution of α-Syn within the cells, with homogeneous regions indicative of monomeric α-Syn and punctated regions, suggesting the formation of oligomers...
March 14, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38483181/structures-and-dynamics-of-%C3%AE-rich-oligomers-of-attr-105-115-assembly
#19
JOURNAL ARTICLE
Liqun Liang, Yuqi Zhang, Yanyan Zhu, Juxia Bai, Yangyang Ni, Junfeng Wan, Haiyan Yue, Qingjie Zhao, Huiyu Li
Transthyretin (TTR) is a tetrameric homologous protein that can dissociate into monomers. Misfolding and aggregation of TTR can lead to amyloid transthyretin amyloidosis (ATTR), which can cause many diseases (e.g., senile systemic amyloidosis, familial amyloid cardiomyopathy, and familial amyloid polyneuropathy). Despite growing evidence indicating that small oligomers play a critical role in regulating cytotoxicity, the structures of these oligomeric intermediates and their conformational transformations are still unclear, impeding our understanding of neurodegenerative mechanisms and the development of therapeutics targeting early aggregation species...
March 14, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38478848/still-in-search-for-an-eaat-activator-gt949-does-not-activate-eaat2-nor-eaat3-in-impedance-and-radioligand-uptake-assays
#20
JOURNAL ARTICLE
Lieve van Veggel, Tamara A M Mocking, Hubert J Sijben, Rongfang Liu, Marina Gorostiola González, Majlen A Dilweg, Jeroen Royakkers, Anna Li, Vijay Kumar, Yin Yao Dong, Alex Bullock, David B Sauer, Hanne Diliën, Gerard J P van Westen, Rudy Schreiber, Laura H Heitman, Tim Vanmierlo
Excitatory amino acid transporters (EAATs) are important regulators of amino acid transport and in particular glutamate. Recently, more interest has arisen in these transporters in the context of neurodegenerative diseases. This calls for ways to modulate these targets to drive glutamate transport, EAAT2 and EAAT3 in particular. Several inhibitors (competitive and noncompetitive) exist to block glutamate transport; however, activators remain scarce. Recently, GT949 was proposed as a selective activator of EAAT2, as tested in a radioligand uptake assay...
March 13, 2024: ACS Chemical Neuroscience
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