journal
https://read.qxmd.com/read/38477556/patient-derived-blood-brain-barrier-model-for-screening-copper-bis-thiosemicarbazone-complexes-as-potential-therapeutics-in-alzheimer-s-disease
#21
JOURNAL ARTICLE
Joanna M Wasielewska, Kathryn Szostak, Lachlan E McInnes, Hazel Quek, Juliana C S Chaves, Jeffrey R Liddell, Jari Koistinaho, Lotta E Oikari, Paul S Donnelly, Anthony R White
Alzheimer's disease (AD) is the most prevalent cause of dementia characterized by a progressive cognitive decline. Addressing neuroinflammation represents a promising therapeutic avenue to treat AD; however, the development of effective antineuroinflammatory compounds is often hindered by their limited blood-brain barrier (BBB) permeability. Consequently, there is an urgent need for accurate, preclinical AD patient-specific BBB models to facilitate the early identification of immunomodulatory drugs capable of efficiently crossing the human AD BBB...
March 13, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38472087/alleviating-severe-cytoskeletal-destruction-of-spinal-motor-neurons-another-effect-of-docosahexaenoic-acid-in-spinal-cord-injury
#22
JOURNAL ARTICLE
Qinqin Pei, Qiurong Zhao, Chunhui Lang, Shilong Feng, Juanjuan Meng, Guangjiao Tan, Wei Cui, Cheng Zhang, Xiaohe Luo, Lixin Xu, Jian Chen
Spinal cord injury (SCI) treatment remains a major challenge. Spinal motor neurons (MNs) are seriously injured in the early stage after SCI, but this has not received sufficient attention. Oxidative stress is known to play a crucial role in SCI pathology. Our studies demonstrated that oxidative stress can cause severe damage to the cytoskeleton of spinal MNs. Docosahexaenoic acid (DHA) has been shown to have beneficial effects on SCI, but the mechanism remains unclear, and no study has investigated the effect of DHA on oxidative stress-induced spinal MN injury...
March 12, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38466778/rational-design-of-tdp-43-derived-%C3%AE-helical-peptide-inhibitors-an-in-silico-strategy-to-prevent-tdp-43-aggregation-in-neurodegenerative-disorders
#23
JOURNAL ARTICLE
Muthu Raj Salaikumaran, Pallavi P Gopal
TDP-43, an essential RNA/DNA-binding protein, is central to the pathology of neurodegenerative diseases, such as amyotrophic lateral sclerosis and frontotemporal dementia. Pathological mislocalization and aggregation of TDP-43 disrupt RNA splicing, mRNA stability, and mRNA transport, thereby impairing neuronal function and survival. The formation of amyloid-like TDP-43 filaments is largely facilitated by the destabilization of an α-helical segment within the disordered C-terminal region. In this study, we hypothesized that preventing the destabilization of the α-helical domain could potentially halt the growth of these pathological filaments...
March 11, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38462729/kynurenines-dynamics-in-the-periphery-and-central-nervous-system-steers-behavioral-deficits-in-rats-under-hypobaric-hypoxia
#24
JOURNAL ARTICLE
Kalyani Verma, Amitabh, Dipti N Prasad, M Prasanna Kumar Reddy, Ekta Kohli
People travel to high-altitude regions as tourists, workers, and military personnel on duty. Despite the consistent 21% oxygen content in the atmosphere, ascending to higher altitudes results in a decrease in the partial pressure of oxygen, inducing a state known as hypobaric hypoxia (HH). HH is an environmental stress that is responsible for neuroinflammation and behavioral deficits (anxiety, depression, mood disturbance, etc.), but little is known about its metabolic pathways. The kynurenine pathway (KP) is a promising candidate to uncover the mysteries of HH stress, as it is an important regulator of the immune system and is associated with behavioral deficits...
March 10, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38457777/-18-f-labeled-pet-tracers-specific-for-adenosine-a-2a-receptor-design-synthesis-and-biological-evaluation
#25
JOURNAL ARTICLE
Tingyu Yang, Wei Zheng, Xuebo Cheng, Hualong Chen, Zeng Jiang, Ziyue Yu, Lu Zhang, Yi Xie, Lianjie Du, Xuan Ge, Jiahuai Zhang, Leilei Yuan, Yajing Liu, Zehui Wu
By modifying the structures of targeted A2A R antagonists and tracers, novel compounds 3 , 7a , 9 , 12c , and BIBD-399 were designed and synthesized. In vitro inhibition experiments demonstrated that 3 , 12c , and BIBD-399 have high affinity for A2A R. [ 18 F]3 and [18 F]BIBD-399 were successfully synthesized. In terms of biological distribution, the brain uptake of [18 F]MNI-444 exhibits greater than that of [ 18 F]3 and [18 F]BIBD-399. PET imaging shows that [ 18 F]3 is off-target in the brain, while [18 F]BIBD-399 and [18 F]MNI-444 can be specifically imaged in regions with high A2A R expression...
March 8, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38454572/aryl-hydrocarbon-receptor-involvement-in-the-sodium-dependent-glutamate-aspartate-transporter-regulation-in-cerebellar-bergmann-glia-cells
#26
JOURNAL ARTICLE
Janisse Silva-Parra, Leticia Ramírez-Martínez, Cecilia Palafox-Gómez, Cristina Sandu, Esther López-Bayghen, Libia Vega, Guillermo Elizondo, Jaqueline Loaeza-Loaeza, Daniel Hernández-Sotelo, Luisa C Hernández-Kelly, Marie-Paule Felder-Schmittbuhl, Arturo Ortega
Glutamate, the major excitatory neurotransmitter in the vertebrate brain, exerts its functions through the activation of specific plasma membrane receptors and transporters. Overstimulation of glutamate receptors results in neuronal cell death through a process known as excitotoxicity. A family of sodium-dependent glutamate plasma membrane transporters is responsible for the removal of glutamate from the synaptic cleft, preventing an excitotoxic insult. Glial glutamate transporters carry out more than 90% of the brain glutamate uptake activity and are responsible for glutamate recycling through the GABA/Glutamate/Glutamine shuttle...
March 7, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38453668/discovery-structure-based-modification-in-vitro-in-vivo-and-in-silico-exploration-of-m-sulfamoyl-benzoamide-derivatives-as-selective-butyrylcholinesterase-inhibitors-for-treating-alzheimer-s-disease
#27
JOURNAL ARTICLE
Xin Lu, Yueqing Li, Qianwen Guan, Huajing Yang, Yijun Liu, Chenxi Du, Lei Wang, Qinghua Wang, Yuqiong Pei, Liang Wu, Haopeng Sun, Yao Chen
For the potential therapy of Alzheimer's disease (AD), butyrylcholinesterase (BChE) has gradually gained worldwide interest in the progression of AD. This study used a pharmacophore-based virtual screening (VS) approach to identify Z32439948 as a new BChE inhibitor. Aiding by molecular docking and molecular dynamics, essential binding information was disclosed. Specifically, a subpocket was found and structure-guided design of a series of novel compounds was conducted. Derivatives were evaluated in vitro for cholinesterase inhibition and physicochemical properties (BBB, log  P , and solubility)...
March 7, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38451201/neuroprotection-role-of-vitamin-c-by-upregulating-glutamate-transporter-1-in-auditory-cortex-of-noise-induced-tinnitus-animal-model
#28
JOURNAL ARTICLE
Wanxin Cao, Shan Xiong, Wenliang Ji, Huan Wei, Furong Ma, Lanqun Mao
Vitamin C (Vc) plays a pivotal role in a series of pathological processes, such as tumors, immune diseases, and neurological disorders. However, its therapeutic potential for tinnitus management remains unclear. In this study, we find that Vc relieves tinnitus in noise-exposed rats. In the 7-day therapy groups, spontaneous firing rate (SFR) increases from 1.17 ± 0.10 Hz to 1.77 ± 0.15 Hz after noise exposure. Vc effectively reduces the elevated SFR to 0.99 ± 0.07 and 0.55 ± 0.05 Hz at different doses...
March 7, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38449097/nav1-7-modulator-bearing-a-3-hydroxyindole-backbone-holds-the-potential-to-reverse-neuropathic-pain
#29
JOURNAL ARTICLE
Yuwei Wang, Jirong Shu, Haoyi Yang, Kemiao Hong, Xiangji Yang, Weijie Guo, Jie Fang, Fuyi Li, Tao Liu, Zhiming Shan, Taoda Shi, Song Cai, Jian Zhang
Chronic pain is a growing global health problem affecting at least 10% of the world's population. However, current chronic pain treatments are inadequate. Voltage-gated sodium channels (Navs) play a pivotal role in regulating neuronal excitability and pain signal transmission and thus are main targets for nonopioid painkiller development, especially those preferentially expressed in dorsal root ganglial (DRG) neurons, such as Nav1.6, Nav1.7, and Nav1.8. In this study, we screened in virtual hits from dihydrobenzofuran and 3-hydroxyoxindole hybrid molecules against Navs via a veratridine (VTD)-based calcium imaging method...
March 6, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38445984/eb1-increases-the-dynamics-of-tau-droplets-and-inhibits-tau-aggregation-implications-in-tauopathies
#30
JOURNAL ARTICLE
Anuradha Venkatramani, Anvesh Ashtam, Dulal Panda
EB1, a microtubule plus end-tracking protein (+TIP), regulates microtubule dynamics. Recent evidence indicates cross-talk between EB proteins and tau, a microtubule-associated neuronal protein that is important for the growth and stability of microtubules. We investigated the interaction between tau and EB1 and the effect of binding of EB1 on tau function and aggregation. EB1 colocalized with tau in SH-SY5Y cells and coimmunoprecipitated with tau. Further, purified EB1 impaired the ability of adult tau to induce tubulin polymerization in vitro ...
March 6, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38445956/phytic-acid-maintains-peripheral-neuron-integrity-and-enhances-survivability-against-platinum-induced-degeneration-via-reducing-reactive-oxygen-species-and-enhancing-mitochondrial-membrane-potential
#31
JOURNAL ARTICLE
Arjun Prasad Tiwari, Bayne Albin, Khayzaran Qubbaj, Prashant Adhikari, In Hong Yang
Phytic acid (PA) has been reported to possess anti-inflammatory and antioxidant properties that are critical for neuroprotection in neuronal disorders. This raises the question of whether PA can effectively protect sensory neurons against chemotherapy-induced peripheral neuropathy (CIPN). Peripheral neuropathy is a dose-limiting side effect of chemotherapy treatment often characterized by severe and abnormal pain in hands and feet resulting from peripheral nerve degeneration. Currently, there are no effective treatments available that can prevent or cure peripheral neuropathies other than symptomatic management...
March 6, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38440987/4-oxypiperidine-ethers-as-multiple-targeting-ligands-at-histamine-h-3-receptors-and-cholinesterases
#32
JOURNAL ARTICLE
Beata Michalska, Marek Dzięgielewski, Justyna Godyń, Tobias Werner, Marek Bajda, Tadeusz Karcz, Katarzyna Szczepańska, Holger Stark, Anna Więckowska, Krzysztof Walczyński, Marek Staszewski
This study examines the properties of a novel series of 4-oxypiperidines designed and synthesized as histamine H3 R antagonists/inverse agonists based on the structural modification of two lead compounds, viz., ADS003 and ADS009 . The products are intended to maintain a high affinity for H3 R while simultaneously inhibiting AChE or/and BuChE enzymes. Selected compounds were subjected to h H3 R radioligand displacement and gp H3 R functional assays. Some of the compounds showed nanomolar affinity. The most promising compound in the naphthalene series was ADS031 , which contained a benzyl moiety at position 1 of the piperidine ring and displayed 12...
March 5, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38436259/deciphering-the-association-of-epstein-barr-virus-and-its-glycoprotein-m-peptide-with-neuropathologies-in-mice
#33
JOURNAL ARTICLE
Annu Rani, Priyanka Patra, Tarun Prakash Verma, Anamika Singh, Ajay Kumar Jain, Neha Jaiswal, Sanjeev Narang, Nitish Mittal, Hamendra Singh Parmar, Hem Chandra Jha
The reactivation of ubiquitously present Epstein-Barr virus (EBV) is known to be involved with numerous diseases, including neurological ailments. A recent in vitro study from our group unveiled the association of EBV and its 12-amino acid peptide glycoprotein M146-157 (gM146-157 ) with neurodegenerative diseases, viz., Alzheimer's disease (AD) and multiple sclerosis. In this study, we have further validated this association at the in vivo level. The exposure of EBV/gM146-157 to mice causes a decline in the cognitive ability with a concomitant increase in anxiety-like symptoms through behavioral assays...
March 4, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38433715/reversible-morphological-remodeling-of-prefrontal-and-hippocampal-serotonergic-fibers-by-fluoxetine
#34
JOURNAL ARTICLE
Serena Nazzi, Marta Picchi, Sara Migliarini, Giacomo Maddaloni, Noemi Barsotti, Massimo Pasqualetti
Serotonin-releasing fibers depart from the raphe nuclei to profusely innervate the entire central nervous system, displaying in some brain regions high structural plasticity in response to genetically induced abrogation of serotonin synthesis. Chronic fluoxetine treatment used as a tool to model peri-physiological, clinically relevant serotonin elevation is also able to cause structural rearrangements of the serotonergic fibers innervating the hippocampus. Whether this effect is limited to hippocampal-innervating fibers or extends to other populations of axons is not known...
March 4, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38433380/modulation-of-primary-and-secondary-processes-in-tau-fibril-formation-by-salt-induced-dynamics
#35
JOURNAL ARTICLE
Arshad Abdul Vahid, Muhammed Shafeek Oliyantakath Hassan, Allwin Ebenezer Sahayaraj, Ann Teres Babu, Safwa T Kizhakkeduth, Vinesh Vijayan
The initial stages of amyloid fibrilization begin with the monomers populating aggregation-prone conformers. Characterization of such aggregation-prone conformers is crucial in the study of neurodegenerative diseases. The current study characterizes the aggregation pathway of two tau protein constructs that have been recently demonstrated to form Alzheimer's (AD) fibril structures with divalent ions and chronic traumatic encephalopathy (CTE) fibril structures with monovalent ions. The results highlight the involvement of identical residues in both the primary and secondary processes of both AD and CTE fibril propagation...
March 3, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38421952/a-toxicogenic-interaction-between-intracellular-amyloid-%C3%AE-and-apolipoprotein-e
#36
JOURNAL ARTICLE
Arpan Dey, Aditi Verma, Uchit Bhaskar, Bidyut Sarkar, Mamata Kallianpur, Vicky Vishvakarma, Anand Kant Das, Kanchan Garai, Odity Mukherjee, Kunihiko Ishii, Tahei Tahara, Sudipta Maiti
Alzheimer's disease (AD) is associated with the aggregation of amyloid β (Aβ) and tau proteins. Why ApoE variants are significant genetic risk factors remains a major unsolved puzzle in understanding AD, although intracellular interactions with ApoE are suspected to play a role. Here, we show that specific changes in the fluorescence lifetime of fluorescently tagged small Aβ oligomers in rat brain cells correlate with the cellular ApoE content. An inhibitor of the Aβ-ApoE interaction suppresses these changes and concomitantly reduces Aβ toxicity in a dose-dependent manner...
February 29, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38421943/sex-specific-transcriptomic-changes-in-the-villous-tissue-of-placentas-of-pregnant-women-using-a-selective-serotonin-reuptake-inhibitor
#37
JOURNAL ARTICLE
Laura Staal, Torsten Plösch, Theodora Kunovac Kallak, Inger Sundström Poromaa, Bregje Wertheim, Jocelien D A Olivier
About 5% of pregnant women are treated with selective serotonin reuptake inhibitor (SSRI) antidepressants to treat their depression. SSRIs influence serotonin levels, a key factor in neural embryonic development, and their use during pregnancy has been associated with adverse effects on the developing embryo. However, the role of the placenta in transmitting these negative effects is not well understood. In this study, we aim to elucidate how disturbances in the maternal serotonergic system affect the villous tissue of the placenta by assessing whole transcriptomes in the placentas of women with healthy pregnancies and women with depression and treated with the SSRI fluoxetine during pregnancy...
February 29, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38420772/potential-metabolite-biomarkers-of-multiple-sclerosis-from-multiple-biofluids
#38
JOURNAL ARTICLE
Fatema Bhinderwala, Heidi E Roth, Mary Filipi, Samantha Jack, Robert Powers
Multiple sclerosis (MS) is a chronic and progressive neurological disorder without a cure, but early intervention can slow disease progression and improve the quality of life for MS patients. Obtaining an accurate diagnosis for MS is an arduous and error-prone task that requires a combination of a detailed medical history, a comprehensive neurological exam, clinical tests such as magnetic resonance imaging, and the exclusion of other possible diseases. A simple and definitive biofluid test for MS does not exist, but is highly desirable...
February 29, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38416693/a-relationship-between-the-structures-and-neurotoxic-effects-of-a%C3%AE-oligomers-stabilized-by-different-metal-ions
#39
JOURNAL ARTICLE
Sean Chia, Rodrigo Lessa Cataldi, Francesco Simone Ruggeri, Ryan Limbocker, Itzel Condado-Morales, Katarina Pisani, Andrea Possenti, Sara Linse, Tuomas P J Knowles, Johnny Habchi, Benedetta Mannini, Michele Vendruscolo
Oligomeric assemblies of the amyloid β peptide (Aβ) have been investigated for over two decades as possible neurotoxic agents in Alzheimer's disease. However, due to their heterogeneous and transient nature, it is not yet fully established which of the structural features of these oligomers may generate cellular damage. Here, we study distinct oligomer species formed by Aβ40 (the 40-residue form of Aβ) in the presence of four different metal ions (Al3+ , Cu2+ , Fe2+ , and Zn2+ ) and show that they differ in their structure and toxicity in human neuroblastoma cells...
February 28, 2024: ACS Chemical Neuroscience
https://read.qxmd.com/read/38416107/reduction-of-amyloid-%C3%AE-production-without-inhibiting-secretase-activity-by-ms-275
#40
JOURNAL ARTICLE
Yachiyo Mitsuishi, Masaki Nakano, Hirotatsu Kojima, Takayoshi Okabe, Masaki Nishimura
Brain amyloid-β (Aβ) governs the pathogenic process of Alzheimer's disease. Clinical trials to assess the disease-modifying effects of inhibitors or modulators of β- and γ-secretases have not shown clinical benefit and can cause serious adverse events. Previously, we found that the interleukin-like epithelial-to-mesenchymal transition inducer (ILEI, also known as FAM3C) negatively regulates the Aβ production through a decrease in Aβ immediate precursor, without the inhibition of β- and γ-secretase activity...
February 28, 2024: ACS Chemical Neuroscience
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