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ACS Chemical Neuroscience

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https://www.readbyqxmd.com/read/28933530/future-priorities-in-tackling-infections-due-to-brain-eating-amoebae
#1
Naveed Ahmed Khan, Ayaz Anwar, Ruqaiyyah Siddiqui
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 key priorities for improving outcomes from infections due to brain-eating amoebae.
September 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28933527/caring-about-power-analyses
#2
Jennifer E Murray, Scott T Barrett, Rebecca L Brock, Rick A Bevins
Everyone should care deeply about statistical power and effect size given that the current estimates of wasted nonreproducible and exaggerated research findings range from 50 to 85%, combined with the mandates from the National Institutes of Health (NIH) that proposal reviewers focus on scientific rigor and investigators consider sex as a biological variable. In this Viewpoint, we provide recommendations and resources regarding power analyses aimed at enhancing rigor, and hence decreasing waste, when designing experiments...
September 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28857544/identification-of-5-1-methyl-5-trifluoromethyl-1h-pyrazol-3-yl-thiophene-2-carboxamides-as-novel-and-selective-monoamine-oxidase-b-inhibitors-used-to-improve-memory-and-cognition
#3
Alan P Kaplan, Terence Keenan, Roderick Scott, Xianbo Zhou, Rusiko Bourchouladze, Andrew J McRiner, Mark E Wilson, Darlene Romashko, Regina Miller, Matthew Bletsch, Gary Anderson, Jennifer Stanley, Adia Zhang, Dong Lee, John Nikpur
Initial work in Drosophila and mice demonstrated that the transcription factor cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) is a master control gene for memory formation. The relationship between CREB and memory has also been found to be true in other species, including aplysia and rats. It is thus well-established that CREB activation plays a central role in memory enhancement and that CREB is activated during memory formation. On the basis of these findings, a phenotypic high-throughput screening campaign utilizing a CRE-luciferase (CRE-Luci) SK-N-MC cell line was performed to identify compounds that enhance transcriptional activation of the CRE promoter with a suboptimal dose of forskolin...
September 20, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28925253/novel-trimodal-maldi-imaging-mass-spectrometry-ims3-at-10-%C3%AE-m-reveals-spatial-lipid-and-peptide-correlates-implicated-in-a%C3%AE-plaque-pathology-in-alzheimer-s-disease
#4
Ibrahim Kaya, Dimitri Brinet, Wojciech Michno, Mehmet Baskurt, Henrik Zetterberg, Kaj Blennow, Jörg Hanrieder
Multimodal chemical imaging using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) can provide comprehensive molecular information in situ within the same tissue sections. This is of relevance for studying different brain pathologies such as Alzheimer's Disease (AD), where recent data suggest a critical relevance of co-localizing Aβ peptides and neuronal lipids. We here developed a novel trimodal, high-resolution (10µm) MALDI imaging MS (IMS) paradigm for negative- and positive ion mode lipid analysis and subsequent protein ion imaging on the same tissue section...
September 19, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28872831/novel-vilazodone-tacrine-hybrids-as-potential-multitarget-directed-ligands-for-the-treatment-of-alzheimer-s-disease-accompanied-with-depression-design-synthesis-and-biological-evaluation
#5
Xiaokang Li, Huan Wang, Yixiang Xu, Wenwen Liu, Qi Gong, Wei Wang, Xiaoxia Qiu, Jin Zhu, Fei Mao, Haiyan Zhang, Jian Li
Depression is one of the most frequent psychiatric complications of Alzheimer's disease (AD), affecting up to 50% of the patients. A novel series of hybrid molecules were designed and synthesized by combining the pharmacophoric features of vilazodone and tacrine as potential multitarget-directed ligands for the treatment of AD with depression. In vitro biological assays were conducted to evaluate the compounds; among the 30 hybrids, compound 1e showed relatively balanced profiles between acetylcholinesterase inhibition (IC50 = 3...
September 19, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28914525/two-distinct-polymorphic-folding-states-of-self-assembly-of-the-non-amyloid-%C3%AE-component-differ-in-the-arrangement-of-the-residues
#6
Maya Pollock-Gagolashvili, Yifat Miller
Parkinson's disease is a degenerative disorder of the central nerves system. It is characterized by presence of Lew bodies (LBs), in which the main components of the LBs are α-synuclein (AS) aggregates. The central domain of AS, known as the "non-amyloid β component" (NAC) is responsible for the aggregation properties of AS. It is proposed that AS fibrillar structure is a well-packed cross-β structure of the NAC domains, while the N- and C-termini are disordered. Therefore, the study of the self-assembly of NAC domains are crucial in order to understand the molecular mechanisms of AS aggregation...
September 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28862431/the-medicinal-chemistry-of-natural-and-semisynthetic-compounds-against-parkinson-s-and-huntington-s-diseases
#7
Enrico Zanforlin, Giuseppe Zagotto, Giovanni Ribaudo
Among the diseases affecting the central nervous system (CNS), neurodegenerations attract the interest of both the clinician and the medicinal chemist. The increasing average age of population, the growing number of patients, and the lack of long-term effective remedies push ahead the quest for novel tools against this class of pathologies. We present a review on the state of the art of the molecules (or combination of molecules) of natural origin that are currently under study against two well-defined pathologies: Parkinson's disease (PD) and Huntington's disease (HD)...
September 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28817252/experimental-and-theoretical-insights-into-the-inhibition-mechanism-of-prion-fibrillation-by-resveratrol-and-its-derivatives
#8
Lanlan Li, Yongchang Zhu, Shuangyan Zhou, Xiaoli An, Yan Zhang, Qifeng Bai, Yong-Xing He, Huanxiang Liu, Xiaojun Yao
Resveratrol and its derivatives have been shown to display beneficial effects to neurodegenerative diseases. However, the molecular mechanism of resveratrol and its derivatives on prion conformational conversion is poorly understood. In this work, the interaction mechanism between prion and resveratrol as well as its derivatives was investigated using steady-state fluorescence quenching, Thioflavin T binding assay, Western blotting, and molecular dynamics simulation. Protein fluorescence quenching method and Thioflavin T assay revealed that resveratrol and its derivatives could interact with prion and interrupt prion fibril formation...
September 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28906103/resolving-the-atomistic-modes-of-anle138b-inhibitory-action-on-peptide-oligomer-formation
#9
Dirk Matthes, Vytautas Gapsys, Christian Griesinger, Bert L de Groot
The di-phenyl-pyrazole compound anle138b is a known inhibitor of oligomeric aggregate formation in vitro and in vivo. Therefore, anle138b is considered a promising drug candidate to beneficially interfere with neurodegenerative processes causing devastating pathologies in humans. The atomistic details of the aggregation inhibition mechanism, however, are to date unknown since the ensemble of small nonfibrillar aggregates is structurally heterogeneous and inaccessible to direct structural characterization. Here, we set out to elucidate anle138b's mode of action using all-atom molecular dynamics simulations on the multi-microsecond timescale...
September 14, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28902487/angiostrongylus-cantonensis-agent-of-a-sometimes-fatal-globally-emerging-infectious-disease-rat-lungworm-disease
#10
Robert H Cowie
Angiostrongylus cantonensis, the rat lungworm, is a dangerous invasive species that is the agent of a potentially fatal globally emerging infectious disease. Humans are infected most commonly by ingestion, deliberately or inadvertently, of the parasite larvae in their intermediate snail hosts. The larvae make their way to the brain where they can cause severe neurological damage before eventually dying. Symptoms of the disease are diverse, making it difficult to diagnose. Treatment is primarily with corticosteroids to reduce inflammation, while treatment with anthelmintics to kill the worms remains controversial...
September 13, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28901737/melatonin-improves-cognitive-deficits-via-restoration-of-cholinergic-dysfunction-in-a-mouse-model-of-scopolamine-induced-amnesia
#11
Bai Hui Chen, Joon Ha Park, Dae Won Kim, Jinseu Park, Soo Young Choi, In Hye Kim, Jeong Hwi Cho, Tae-Kyeong Lee, Jae Chul Lee, Choong-Hyun Lee, In Koo Hwang, Young-Myeong Kim, Bing Chun Yan, Il-Jun Kang, Bich Na Shin, Yun Lyul Lee, Myoung Cheol Shin, Jun Hwi Cho, Young Joo Lee, Yong Hwan Jeon, Moo-Ho Won, Ji Hyeon Ahn
Melatonin is known to improve cognitive deficits and its functions have been studied in various disease models, including Alzheimer's disease. In this study, we investigated effects of melatonin on cognition and the cholinergic system of the septum and hippocampus in a mouse model of scopolamine-induced amnesia. Scopolamine (1 mg/kg) and melatonin (10 mg/kg) were administered intraperitoneally to mice for 2 and 4 weeks. The Morris water maze and passive avoidance tests revealed that both treatments of scopolamine significantly impaired spatial learning and memory; however, 2- and 4-week melatonin treatments significantly improved the spatial learning and memory...
September 13, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28898051/effect-of-alzheimer-familial-chromosomal-mutations-on-the-amyloid-fibril-interaction-with-different-pet-tracers-insight-from-molecular-modeling-studies
#12
Kanagasabai Balamurugan, Natarajan Arul Murugan, Bengt Långström, Agneta Nordberg, Hans Ågren
Alzheimer's disease (AD) is the most common neurodegenerative disorder. Along with an increasing number of elderly worldwide it poses a great challenge for the society and healthcare. Although sporadic AD is the common form of AD, 2-3% of the AD cases are expected to be due to mutations in the beta region of the amyloid precursor protein which is referred to as autosomal dominant AD (ADAD). These mutations may cause changes in the secondary structure of the amyloid beta fibrils and may alter the fibrillization rate leading to changes in the disease development and could also affect the binding to tracers used in diagnosis...
September 12, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28885007/stereoselective-differences-between-the-reinforcing-and-motivational-effects-of-cathinone-derived-4-methylmethcathinone-mephedrone-in-self-administering-rats
#13
Helene L Philogene-Khalid, Steven J Simmons, Sunil Nayak, Rose M Martorana, Shu H Su, Yohanka Caro, Brona Ranieri, Kathryn DiFurio, Lili Mo, Taylor A Gentile, Ali Murad, Allen B Reitz, John W Muschamp, Scott M Rawls
Mephedrone (4-methylmethcathinone (4-MMC)) (MEPH) is a new psychoactive substance (NPS) of the synthetic cathinone class. MEPH has a chiral center and exists as two enantiomers (R-,S-MEPH), yet stereospecific effects of MEPH have not been extensively investigated in preclinical assays. Because significant behavioral and neurochemical differences can exist between enantiomers, probing effects of stereochemistry on biological activity enables separation of adverse and therapeutic effects. Our prior work showed that R-MEPH, relative to S-MEPH, produced greater locomotor activation, place preference and facilitation of brain reward thresholds in rodents...
September 8, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28825789/multifunctional-analogs-of-kynurenic-acid-for-the-treatment-of-alzheimer-s-disease-synthesis-pharmacology-and-molecular-modeling-studies
#14
Girdhar Singh Deora, Srinivas Kantham, Stephen Chan, Satish N Dighe, Suresh K Veliyath, Gawain McColl, Marie-Odile Parat, Ross P McGeary, Benjamin P Ross
We report the synthesis and pharmacological investigation of analogs of the endogenous molecule kynurenic acid (KYNA) as multifunctional agents for the treatment of Alzheimer's disease (AD). Synthesized KYNA analogs were tested for their N-methyl-d-aspartate (NMDA) receptor binding, mGluR5 binding and function, acetylcholinesterase (AChE) inhibition, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, interference with the amyloid β peptide (Aβ) fibrillation process, and protection against Aβ-induced toxicity in transgenic Caenorhabditis elegans strain GMC101 expressing full-length Aβ42...
September 8, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28880525/mitoneet-cisd1-knockout-mice-show-signs-of-striatal-mitochondrial-dysfunction-and-a-parkinson-s-disease-phenotype
#15
Werner J Geldenhuys, Stanley A Benkovic, Li Lin, Heather M Yonutas, Samuel D Crish, Patrick G Sullivan, Altaf S Darvesh, Candice M Brown, Jason Richardson
Mitochondrial dysfunction is thought to play a significant role in neurodegeneration observed in Parkinson's disease (PD), yet the mechanisms underlying this pathology remain unclear. Here, we demonstrate that loss of mitoNEET (CISD1), an iron-sulfur containing protein which regulates mitochondrial bioenergetics, results in mitochondrial dysfunction and loss of striatal dopamine and tyrosine hydroxylase. Mitochondria isolated from mice lacking mitoNEET were dysfunctional as revealed by elevated reactive oxygen species (ROS) and reduced capacity to produce ATP...
September 7, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28880522/correction-to-vitamin-derived-nanolipoidal-carriers-for-brain-delivery-of-dimethyl-fumarate-a-novel-approach-with-preclinical-evidence
#16
Pramod Kumar, Gajanand Sharma, Rajendra Kumar, Ruchi Malik, Bhupinder Singh, O P Katare, Kaisar Raza
No abstract text is available yet for this article.
September 7, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28841372/vitamin-b12-inhibits-tau-fibrillization-via-binding-to-cysteine-residues-of-tau
#17
Saharnaz Rafiee, Kazem Asadollahi, Gholamhossein Riazi, Shahin Ahmadian, Ali Akbar Saboury
Two mechanisms underlie the inhibitory/acceleratory action of chemical compounds on tau aggregation including the regulation of cellular kinases and phosphatases activity and direct binding to tau protein. Vitamin B12 is one of the tau polymerization inhibitors, and its deficiency is linked to inactivation of protein phosphatase 2A and subsequently hyperphosphorylation and aggregation of tau protein. Regarding the structure and function of vitamin B12 and tau protein, we assumed that vitamin B12 is also able to directly bind to tau protein...
September 6, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28837764/novel-cell-model-for-tauopathy-induced-by-a-cell-permeable-tau-related-peptide
#18
John R Veloria, Lin Li, Gail A M Breen, Warren J Goux
In the present study, a cell penetrating peptide (CPP)-amyloid conjugate was prepared (T-peptide), where the amyloid-forming sequence was homologous to a nucleating sequence from human Tau protein ((306)VQIVYK(311)). Kinetic and biophysical studies showed the peptide formed long-lived oligomers which were taken up by endocytosis and localized in perinuclear vesicles and in the cytoplasm of murine hippocampal neuroblastoma cells and human HeLa cells. Thioflavin S (ThS) staining of amyloid colocalized with pathological phosphorylated Tau, suggesting that the peptide was able to seed endogenous wild-type Tau...
September 6, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28872835/revisiting-the-quinoxalinedione-scaffold-in-the-construction-of-new-ligands-for-the-ionotropic-glutamate-receptors
#19
Charles S Demmer, David Rombach, Na Liu, Birgitte Nielsen, Darryl S Pickering, Lennart Bunch
More than two decades ago, the quinoxalinedione scaffold was shown to act as an α-amino acid bioisoster. Following extensive structure-activity relationship (SAR) studies, the antagonists DNQX, CNQX, and NBQX in the ionotropic glutamate receptor field were identified. In this work, we revisit the quinoxalinedione scaffold and explore the incorporation of an acid functionality in the 6-position. The SAR studies disclose that by this strategy it was possible to tune in iGluR selectivity among the AMPA, NMDA, and KA receptors, and to some extent also obtain full receptor subtype selectivity...
September 5, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28872832/chemically-modified-%C3%AE-amino-3-hydroxy-5-methyl-4-isoxazole-ampa-receptor-rna-aptamers-designed-for-in-vivo-use
#20
Zhen Huang, Wei Wen, Andrew Wu, Li Niu
Glutamate ion channels have three subtypes, that is, α-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA), kainate, and N-methyl-d-aspartate (NMDA) receptors. Excessive activity of these receptor subtypes either individually or collectively is involved in various neurological disorders. RNA aptamers as antagonists of these receptors are potential therapeutics. For developing aptamer therapeutics, the RNA aptamers must be chemically modified to become ribonuclease-resistant or stable in biological fluids. Using systematic evolution of ligands by exponential enrichment (SELEX) and a chemically modified library, prepared enzymatically (i...
September 5, 2017: ACS Chemical Neuroscience
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