Article
Pharmacology & Pharmacy
Maria Pechlivanidou, Elpinickie Ninou, Katerina Karagiorgou, Aikaterini Tsantila, Renato Mantegazza, Andreetta Francesca, Raffaello Furlan, Leon Dudeck, Johann Steiner, John Tzartos, Socrates Tzartos
Summary: In this review, the authors focus on the autoimmunity against neuronal nicotinic acetylcholine receptors (nAChRs), specifically the autoantibodies and their mechanisms in selected autoimmune diseases. They summarize the current knowledge from human diseases and experimental models, highlighting the infrequency of autoimmunity to neuronal nAChRs except for the autoantibodies to the alpha 3 subunit containing nAChR (alpha 3-nAChR). The authors also discuss the presence of autoantibodies to other neuronal nAChR subtypes and the need for further verification.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Medicine, Research & Experimental
Sibah Hasan, Mehreen Ahmed, Sara Garcia-Rates, Susan Greenfield
Summary: A 14mer peptide, T14, is a potential signaling molecule associated with neurodegeneration in Alzheimer's disease. Its effects can be blocked by a cyclised variant called 'NBP14' and a polyclonal antibody called 'Ab-19'. Both NBP14 and Ab-19 show dose-dependent inhibition of T14's effects in PC12 cells. The most delayed and indirect index of T14 action, AChE release, is the least affected by the lowest doses of either NBP14 or Ab-19.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Charlotte Bakker, Samantha Prins, Jan Liptrot, Ellen P. Hart, Erica S. Klaassen, Giles A. Brown, Alastair Brown, Miles Congreve, Malcolm Weir, Fiona H. Marshall, Jasper Stevens, David M. Cross, Tim Tasker, Pradeep J. Nathan, Geert Jan Groeneveld
Summary: HTL0009936 is a selective M-1 muscarinic receptor agonist being developed for cognitive dysfunction in Alzheimer's disease. The pharmacokinetics of HTL0009936 showed dose-proportional increases in exposure with a mean half-life of 2.4 hours, and it was well-tolerated in healthy elderly subjects. However, there were no clear conclusions on the pharmacodynamic effects of HTL0009936.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Tasia Amelia, Jacobus P. D. van Veldhoven, Matteo Falsini, Rongfang Liu, Laura H. Heitman, Gerard J. P. van Westen, Elena Segala, Gregory Verdon, Robert K. Y. Cheng, Robert M. Cooke, Daan van der Es, Adriaan P. IJzerman
Summary: In this study, the crystal structure of an engineered human adenosine A(2A) receptor bound to a partial agonist was determined and compared to structures bound to a full agonist or antagonist/inverse agonist. Interaction between the partial agonist and amino acids in the ligand binding pocket led to the development of a library of derivatives with varied activities. Some derivatives showed partial agonist properties while others acted as inverse agonists, with additional computational docking studies providing insights into this behavior.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Maria Chiara Pismataro, Nicole A. Horenstein, Clare Stokes, Clelia Dallanoce, Ganesh A. Thakur, Roger L. Papke
Summary: NS6740 is a selective partial agonist for the alpha(7) nicotinic acetylcholine receptor, capable of promoting stable conversion of receptors to nonconducting states and reactivation with positive allosteric modulators. Despite its low efficacy for channel activation, it is an effective activator of the cholinergic anti-inflammatory pathway. Experimental results suggest that the unique properties of NS6740 may primarily be due to binding at the sites for orthosteric agonists.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Xin Liu, Zhao-Yan Cheng, Yan-Feng Li, Chao Liu, Xiao-Jian Gong, Ling He
Summary: This study found that the DRD2 agonist bromocriptine can improve A beta 1-42 induced neuroinflammation and memory deficits through the DRD2/beta-arrestin 2/PP2A/JNK signaling axis.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Immunology
Murat Cakir, Furkan Yuksel, Mahmud Mustafa Ozkut, Merve Durhan, Emin Kaymak, Suat Tekin, Yilmaz Cigremis
Summary: This study investigated the effects of TRPV1 agonist capsaicin and antagonist capsazepine on an AD model induced by OKA. The results showed that capsaicin could reverse the pathological changes of neurodegeneration, neuroinflammation, and deterioration in spatial memory caused by ICV OKA administration.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Beatrice Chambraud, Cillian Byrne, Geri Meduri, Etienne Emile Baulieu, Julien Giustiniani
Summary: This review summarizes the importance of FKBP52 in the nervous system, particularly its role in microtubule function and neurodegenerative diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Charlotte Bakker, Tim Tasker, Jan Liptrot, Ellen P. Hart, Erica S. Klaassen, Samantha Prins, Thalia F. Doef, Giles A. Brown, Alastair Brown, Miles Congreve, Malcolm Weir, Fiona H. Marshall, David M. Cross, Geert Jan Groeneveld, Pradeep J. Nathan
Summary: HTL0018318 is a promising selective M-1 receptor partial agonist for the symptomatic treatment of cognitive and behavioural symptoms in Alzheimer's disease and other dementias, showing well-characterized pharmacokinetics and generally good tolerability in the studied dose range. However, there were no statistically significant effects on cognitive function detected in this study.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xiaodong Kong, Yuting Yang, Huijie Li, Weiyun Cui, Xiaohui Wu, Min Gong, Ying Li
Summary: Alzheimer's disease (AD) treatment involves crucially halting the development of neuronal necroptosis and neuroinflammation. Recent research has found that Liraglutide can delay the progression of AD by inhibiting RIPK1-mediated necrosis and microglial activation, suggesting potential therapeutic implications.
INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS
(2021)
Article
Critical Care Medicine
Elliott D. Crouser, Rachel M. Smith, Daniel A. Culver, Mark W. Julian, Karen Martin, Joanne Baran, Christopher Diaz, Barbaros Selnur Erdal, Erinn M. Hade
Summary: Nicotine treatment in patients with active pulmonary sarcoidosis is well tolerated and may lead to improvements in FVC, but has limited impact on other lung function indicators and disease assessment tools.
Article
Neurosciences
Marc R. Plagenhoef, Patrick M. Callahan, Wayne D. Beck, David T. Blake, Alvin V. Terry Jr.
Summary: This study evaluated the cognitive capabilities of rhesus monkeys across different age ranges in various delayed response tasks. Results showed that older monkeys generally performed less proficiently than younger ones, with some older monkeys showing comparable performance while others were significantly impaired. This suggests that older monkeys can be categorized as either cognitively-unimpaired or cognitively-impaired.
Article
Biophysics
Dinesh C. Indurthi, Anthony Auerbach
Summary: This study examines the attributes of agonists, including potency, efficacy, and efficiency, and their relationships with the size of the agonist headgroup. Efficiency of an agonist can be calculated using EC50 and asymptotes derived from a CRC. The research on 20 agonists shows a bimodal distribution of eta-values, with most binding site mutations having minimal impact on acetylcholine efficiency.
BIOPHYSICAL JOURNAL
(2021)
Article
Pharmacology & Pharmacy
Victoria R. Sanders, Neil S. Millar
Summary: Considerable progress has been made in the identification and characterization of subtype-selective modulators of nicotinic acetylcholine receptors (nAChRs), specifically alpha 7 nAChRs. This review focuses on alpha 7-selective modulators that bind to receptor sites other than the orthosteric agonist binding site for acetylcholine. The mechanism of action and binding sites of these modulators is still a topic of debate.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Cell Biology
Wei Zhang, Jigang Wang, Chuanbin Yang
Summary: Alzheimer's disease (AD) is a common neurodegenerative disease with limited effective therapeutics. Autophagy plays a crucial role in AD progression, and enhancing autophagy pathway is a potential strategy to degrade pathological proteins. Celastrol, a natural small molecule, has been found to activate autophagy and improve memory deficits in AD animal models, suggesting it as a novel drug candidate for AD and other tauopathies.
Article
Clinical Neurology
Jennifer M. Walters, Eung Chang Kim, Jiaren Zhang, Han Gil Jeong, Archit Bajaj, Brian C. Baculis, Gregory C. Tracy, Baher Ibrahim, Catherine A. Christian-Hinman, Daniel A. Llano, Graham R. Huesmann, Hee Jung Chung
Summary: This study is the first to demonstrate that the drug TC-2153 has inhibitory effects on hippocampal excitability and seizure severity in both sexes. TC-2153 can reduce seizure severity and decrease overall hippocampal excitability.
Article
Acoustics
Jihun Kim, Mathew R. Lowerison, Nathiya V. Chandra Sekaran, Zhengchang Kou, Zhijie Dong, Michael L. Oelze, Daniel A. Llano, Pengfei Song
Summary: Ultrasound localization microscopy (ULM) shows potential for visualizing tissue microvasculature at depth with high spatial resolution. A novel ULM imaging sequence based on MB uncoupling via transmit excitation (MUTE) is proposed, which silences MB signals to facilitate MB separation and localization, resulting in reduced data acquisition time and improved temporal resolution.
IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL
(2022)
Article
Oncology
Christina Yau, Marie Osdoit, Marieke van der Noordaa, Sonal Shad, Jane Wei, Diane de Croze, Anne-Sophie Harny, Marick Lae, Fabien Reyal, Gabes S. Sonke, Tessa G. Steenbruggen, Maartje van Seijen, Jelle Wesseling, Miguel Martin, Maria del Monte-Millan, Sara Lopez-Tarruella, Judy C. Boughey, Matthew P. Goetz, Tanya Hoskin, Rebekah Gould, Vicente Valero, Stephen B. Edge, Jean E. Abraham, John M. S. Bartlett, Carlos Caldas, Janet Dunn, Helena Earl, Larry Hayward, Louise Hiller, Elena Provenzano, Stephen-John Sammut, Jeremy S. Thomas, David Cameron, Ashley Graham, Peter Hail, Lorna Mackintosh, Fang Fan, Andrew K. Godwin, Kelsey Schwensen, Priyanko Sharma, Angela M. DeMichele, Kimberly Cole, Lajos Pusztai, Mi-Ok Kim, Laura J. van't Veer, Laura J. Esserman, W. Fraser Symmans
Summary: This study analyzed data from multiple independent cohorts to evaluate the relationship between residual cancer burden (RCB) and long-term prognosis in different subtypes of breast cancer. The results showed that higher RCB score was significantly associated with worse event-free survival in all breast cancer subtypes. The study suggests considering the evaluation of RCB as part of standard pathology reporting.
Article
Multidisciplinary Sciences
Matthew R. Lowerison, Nathiya Chandra Sekaran, Wei Zhang, Zhijie Dong, Xi Chen, Daniel A. Llano, Pengfei Song
Summary: Aging-related cognitive decline is a health crisis, with no established mechanism identified. This study used super-resolution ultrasound localization microscopy to image the vasculature of aged mice and found decreased blood velocity, increased vascular tortuosity, and reduced blood volume in the cerebral cortex. These findings provide novel insights into subcortical microvascular dynamics in the aging brain.
SCIENTIFIC REPORTS
(2022)
Article
Psychology, Multidisciplinary
Susanna S. Kwok, Xuan-Mai T. Nguyen, Diana D. Wu, Raksha A. Mudar, Daniel A. Llano
Summary: The association between age-related hearing loss (ARHL) and Alzheimer's Disease (AD) is still poorly understood. A meta-analysis study revealed that AD patients have significantly impaired hearing compared to controls, with a greater effect seen at higher sound frequencies.
FRONTIERS IN PSYCHOLOGY
(2022)
Article
Geriatrics & Gerontology
Lydia T. Nguyen, Elizabeth A. Lydon, Shraddha A. Shende, Daniel A. Llano, Raksha A. Mudar
Summary: Individuals with mild cognitive impairment (MCI) show impaired value-directed strategic processing compared to cognitively normal older adults, as evidenced by behavioral and neural differences.
Article
Neurosciences
David Perez-Gonzalez, Thomas G. Schreiner, Daniel A. Llano, Manuel S. Malmierca
Summary: Age-related hearing loss is a common condition among the elderly, impacting their communication and social participation. Recent studies suggest a possible link between hearing loss and the development of Alzheimer's disease, with changes in acetylcholine playing a role in both hearing deviance detection and Alzheimer's disease. Further research is needed to explore this association.
FRONTIERS IN NEUROSCIENCE
(2022)
Correction
Medicine, Research & Experimental
Pepa Bruce, Kate Ainscough, Lee Hatter, Irene Braithwaite, Lindsay R. Berry, Mark Fitzgerald, Thomas Hills, Kathy Brickell, David Cosgrave, Alex Semprini, Susan Morpeth, Scott Berry, Peter Doran, Paul Young, Richard Beasley, Alistair Nichol
Article
Medicine, Research & Experimental
Pepa Bruce Metadata, Kate Ainscough, Lee Hatter, Irene Braithwaite, Lindsay R. Berry, Mark Fitzgerald, Thomas Hills, Kathy Brickell, David Cosgrave, Alex Semprini, Susan Morpeth, Scott Berry, Peter Doran, Paul Young, Richard Beasley, Alistair Nichol
Summary: This article presents a practical model using Bayesian methods for rapid determination of the effectiveness of prophylactic agents in preventing COVID-19, but recruitment for the actual study did not start due to reduced COVID-19 cases in New Zealand and concerns about the efficacy and risks of HCQ treatment. The model can be easily adapted for other potential prophylactic agents and pathogens, and should be shared and incorporated into future pandemic preparedness planning.
Article
Psychology, Multidisciplinary
Elizabeth A. L. Stine-Morrow, Giavanna S. McCall, Ilber Manavbasi, Shukhan Ng, Daniel A. Llano, Aron K. K. Barbey
Summary: Considerable evidence suggests that language processing depends on memory processes vulnerable to aging declines. This study found that sustained literacy engagement, such as leisure reading, had positive effects on memory and cognition in older adults. The experimental group showed improved verbal working memory, episodic memory, and conceptual integration in sentence processing, regardless of personality characteristics.
FRONTIERS IN PSYCHOLOGY
(2022)
Review
Behavioral Sciences
Silvio Macias, Daniel A. Llano
Summary: This study takes a comparative approach to understand the top-down modulation mechanisms in the mammalian and amphibian inferior colliculus (IC). The key question addressed is whether the thalamotectal projections in mammals and amphibians are homologous and how they interact with projections from the cerebral cortex. The behavioral significance of these descending pathways is also considered, particularly in anurans' ability to navigate complex acoustic landscapes without a corticocollicular projection.
JOURNAL OF COMPARATIVE PHYSIOLOGY A-NEUROETHOLOGY SENSORY NEURAL AND BEHAVIORAL PHYSIOLOGY
(2023)
Article
Neurosciences
Ashwini G. Naik, Robert Kenyon, Aynaz Taheri, Tanya Y. BergerWolf, Baher A. Ibrahim, Yoshitaka Shinagawa, Daniel A. Llano
Summary: Understanding the functional correlations between neuron populations is crucial for studying neuronal networks. V-NeuroStack is a novel network visualization tool that allows visualization of large-scale neuronal activity data. It offers both 3D and 2D visualization modes to explore correlations between neurons and examine specific time steps in detail. It can handle large datasets and potentially support future advancements in data capturing techniques.
JOURNAL OF NEUROSCIENCE RESEARCH
(2023)
Editorial Material
Behavioral Sciences
Peter M. Narins, Daniel A. Llano, Gunther K. H. Zupanc
Summary: This special issue of the Journal of Comparative Physiology A commemorates the life and work of Albert (Al) S. Feng, a pioneer in the field of neuroethology of auditory systems. It includes 15 articles written by friends, students, and colleagues, many of whom have become leading experts themselves in this field. Their contributions provide a comprehensive overview of bioacoustics in amphibians and mammals (including bats) and aim to inspire a new generation of scientists to advance our understanding of brain mechanisms of acoustic perception.
JOURNAL OF COMPARATIVE PHYSIOLOGY A-NEUROETHOLOGY SENSORY NEURAL AND BEHAVIORAL PHYSIOLOGY
(2023)
Article
Geriatrics & Gerontology
Daniel A. Llano, Priya Devanarayan, Viswanath Devanarayan
Summary: This study proposes a framework for classifying and combining biomarkers for Alzheimer's Disease (AD). The researchers found that low levels of VGF in cerebrospinal fluid (CSF) can serve as a strong predictor for the conversion from mild cognitive impairment (MCI) to AD.
NEUROBIOLOGY OF AGING
(2023)
Article
Medicine, General & Internal
Suzanna Kitten, Neel D. Jani, Daniel A. Llano
Summary: Functional neurological symptom disorder is a condition where neurological deficits cannot be explained by medical pathology, and auditory verbal agnosia is one of its manifestations. This case study demonstrates the effectiveness of a multi-pronged treatment approach in resolving conversion symptoms in a 19-year-old patient over several years.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2022)