Article
Biochemistry & Molecular Biology
Hamza Arshad, Zeel Patel, Genki Amano, Le yao Li, Zaid A. M. Al-Azzawi, Surachai Supattapone, Gerold Schmitt-Ulms, Joel C. Watts
Summary: The bank vole prion protein can act as a universal acceptor of prions from different species. Through a cell culture paradigm, it has been found that bank vole prion protein can facilitate cross-species prion replication, and a single amino acid change can alter its permissiveness to prions. This cellular model will be valuable for studying the molecular features of bank vole prion protein as a universal prion acceptor.
JOURNAL OF NEUROCHEMISTRY
(2023)
Review
Immunology
Yan Wang, Limei Cui, He Zhao, Huhuifen He, Liang Chen, Xicheng Song, Dawei Liu, Jingjing Qiu, Yan Sun
Summary: Degenerative diseases have a significant impact on people's life and health, as well as on society. Microglia play a crucial role in neurodegenerative diseases, and inhibiting or activating their functions can effectively control and reduce the occurrence and progression of these diseases.
JOURNAL OF INFLAMMATION RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Yujuan Li, Mengxin Que, Xuan Wang, Gaofeng Zhan, Zhiqiang Zhou, Xiaoxiao Luo, Shiyong Li
Summary: Astrocytes, the most abundant cells in the brain, play a significant role in sleep regulation but their dysfunction may contribute to sleep disorders and increase the risk of other diseases. This review examines the role of astrocytes in sleep disorders, discusses potential mechanisms, and highlights the importance of further research.
Article
Multidisciplinary Sciences
Maximo Sanz-Hernandez, Joseph D. Barritt, Jens Sobek, Simone Hornemann, Adriano Aguzzi, Alfonso De Simone
Summary: The T183A variant of human PrP significantly enhances aggregation propensity, leading to amyloid formation under physiological conditions by the sole C-terminal domain of the protein. The study identified the structural characteristics of the misfolded intermediate promoting aggregation of T183A huPrP and the interactions preventing the population of this species in the wild-type protein, supporting the use of POM antibodies to suppress the aggregation of this amyloidogenic mutant.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Neurosciences
Eiko N. Minakawa, Yoshitaka Nagai
Summary: Polyglutamine diseases are a group of inherited neurodegenerative disorders caused by abnormal expansion of CAG trinucleotide repeats. Stabilizing protein conformation and inhibiting aggregation offer promising therapeutic approaches, while gene silencing to reduce expression of expanded polyQ proteins is another potential treatment avenue. These advancements hold promise for delaying or preventing the progression of currently incurable diseases.
FRONTIERS IN NEUROSCIENCE
(2021)
Review
Nutrition & Dietetics
Lei An, Qiu Lu, Ke Wang, Yousheng Wang
Summary: Urolithins (Uros), gut microbial-derived metabolites, have shown specific advantages in preventing brain aging and age-related brain dysfunctions. However, their usability in diagnosis, prevention, and treatment of neurodegenerative diseases remains unclear.
Review
Nutrition & Dietetics
Umair Shabbir, Muhammad Sajid Arshad, Aysha Sameen, Deog-Hwan Oh
Summary: The gut microbiota can influence brain immune homeostasis through the microbiota-gut-brain axis and play a key role in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). Modulating GM through diet, probiotics, or fecal microbiota transplantation may represent potential therapeutic strategies in treating AD.
Review
Cell Biology
Barbara Tedesco, Leen Vendredy, Vincent Timmerman, Angelo Poletti
Summary: Each protein must be correctly synthesized, folded, and transported to its appropriate location. Failure in these steps can lead to protein misfolding and potential damage. Cells have well-characterized protein quality control systems, including autophagy and chaperone-assisted selective autophagy (CASA), to minimize such issues. The CASA complex, composed of HSPA, HSPB8, and BAG3 proteins, is essential for maintaining protein homeostasis and mutations in these genes can result in (cardio)myopathies and neurodegenerative diseases. This article summarizes the current understanding of the CASA complex and discusses its involvement in diseases and potential therapeutic targets.
Article
Horticulture
Mariana Cecilia Grohar, Barbara Gacnik, Maja Mikulic Petkovsek, Metka Hudina, Robert Veberic
Summary: The study investigated the caffeine content and phenolic profile of different types of teas and coffees with two successive extractions. Green tea showed high flavanol content in the second extraction, while mate tea's phenolic acid content increased. Black tea had the highest caffeine content in both extractions, and water was the most effective solvent in most cases for extracting these compounds.
Review
Geriatrics & Gerontology
Rodrigo Diaz-Espinoza
Summary: Amyloids are highly ordered aggregates composed of proteins or peptides involved in various pathologies, including Alzheimer's and Parkinson's diseases. The specific features of these amyloid structures, such as the Greek-key topology and two-fold symmetry, can serve as novel guides for seeking potential molecular targets in drug design efforts. Advances in solid state NMR and Cryogenic-electron microscopy have allowed the elucidation of these elusive conformations at high resolution.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Review
Nutrition & Dietetics
Zijian Tong, Guodong Chu, Chenmeng Wan, Qiaoyu Wang, Jialing Yang, Zhaoli Meng, Linna Du, Jing Yang, Hongxia Ma
Summary: Mushrooms with edible and medicinal potential have attracted attention due to their diverse biological functions, nutritional value, and delicious taste. Various bioactive substances, including proteins, carbohydrates, phenols, and vitamins, have been identified and purified from mushrooms. Furthermore, molecules derived from mushrooms have shown promise in alleviating the pathological manifestations of Alzheimer's disease (AD), making it important to identify natural products from mushrooms that can modify the progression of AD. This review summarizes recent research on the constituents isolated from mushrooms and their potential in combating AD, as well as the underlying molecular mechanisms involved.
Review
Neurosciences
Sean L. Johnson, Wei-Ling Tsou, Matthew V. Prifti, Autumn L. Harris, Sokol V. Todi
Summary: The presence and aggregation of misfolded proteins have harmful effects on the nervous system, specifically in the family of polyglutamine (polyQ) disorders. These disorders are caused by the abnormal elongation of a polyQ repeat in different proteins, leading to misfolding, aggregation, cellular dysfunction, and diseases. However, each disease is distinct due to the surrounding regions, interacting proteins, and posttranslational modifications. This overview focuses on the control of pathogenicity in the expanded polyQ repeat by non-polyQ regions and explores shared processes and therapeutic entry points for these incurable disorders.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Review
Cell Biology
Shirel Argueti-Ostrovsky, Leenor Alfahel, Joy Kahn, Adrian Israelson
Summary: Multiple neurodegenerative diseases share common cellular and molecular pathological mechanisms, mainly characterized by protein misfolding and aggregation, leading to selective vulnerability of different neurons. Disease progression is accelerated by damage from nonneuronal cells through inflammatory processes.
Article
Biology
Juan R. Coca, Hasier Erana, Joaquin Castilla
Summary: This study delves into the molecular pathways of PrPC and PrPSc proteins, investigating the code of meanings at the molecular level in relation to prion diseases. It also explores potential relationships between prion proteins and other proteins to uncover the semiotic expansion of the PrP code. By analyzing these connections, the study aims to further understand the unusual pathological processes described by Nobel laureate Prusiner.
Review
Biochemistry & Molecular Biology
Sajad Fakhri, Sadaf Abdian, Seyede Nazanin Zarneshan, Esra Kuepeli Akkol, Mohammad Hosein Farzaei, Eduardo Sobarzo-Sanchez
Summary: This review addresses the dysregulated pathways in Parkinson's disease (PD) and proposes the use of plant secondary metabolites to modulate PD-related manifestations, particularly by targeting mitochondria.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Plant Sciences
Yun-Seo Kil, April L. Risinger, Cora L. Petersen, Susan L. Mooberry, Robert H. Cichewicz
JOURNAL OF NATURAL PRODUCTS
(2020)
Article
Plant Sciences
Petra J. Pederson, Shengxin Cai, Chase Carver, Douglas R. Powell, April L. Risinger, Tanja Grkovic, Barry R. O'Keefe, Susan L. Mooberry, Robert H. Cichewicz
JOURNAL OF NATURAL PRODUCTS
(2020)
Article
Plant Sciences
Corena Grant, Shengxin Cai, April L. Risinger, Huiyun Liang, Barry R. O'Keefe, John G. Doench, Robert H. Cichewicz, Susan L. Mooberry
JOURNAL OF NATURAL PRODUCTS
(2020)
Article
Plant Sciences
Hongyan Ma, Huiyun Liang, Shengxin Cai, Barry R. O'Keefe, Susan L. Mooberry, Robert H. Cichewicz
Summary: LLAMAS is an effective platform for natural product discovery, allowing for efficient identification and dereplication of DNA-binding molecules from complex mixtures.
JOURNAL OF NATURAL PRODUCTS
(2021)
Article
Plant Sciences
Jin Woo Lee, Jennifer E. Collins, Karen L. Wendt, Debopam Chakrabarti, Robert H. Cichewicz
Summary: Malaria, affecting over 200 million people annually, remains a global threat. Through systematic testing of fungal extracts from the University of Oklahoma Citizen Science Soil Collection Program, bioactive compounds with potent antiplasmodial activity and low toxicity against human cells were identified, with a new metabolite, harzianin NPDG I, showing remarkable potency and selectivity. This study highlights the potential of fungal diversity in developing novel anti-malarial compounds.
JOURNAL OF NATURAL PRODUCTS
(2021)
Article
Biochemistry & Molecular Biology
Chang-Kwon Kim, Lauren R. H. Krumpe, Emily Smith, Curtis J. Henrich, Isaac Brownell, Karen L. Wendt, Robert H. Cichewicz, Barry R. O'Keefe, Kirk R. Gustafson
Summary: A new linear peptide named roseabol A (1) and a known compound 13-oxo-trans-9,10-epoxy-11(E)-octadecenoic acid (2) were isolated from the fungus Clonostachys rosea. Roseabol A (1) contains amino acid residues characteristic of the peptaibol family of peptides, while compound 2 showed inhibitory activity against Merkel cell carcinoma.
Article
Chemistry, Medicinal
Jennifer E. Collins, Jin Woo Lee, Monica J. Bohmer, Joshua D. Welden, Arash K. Arshadi, Lin Du, Robert H. Cichewicz, Debopam Chakrabarti
Summary: The study presented a series of cyclic tetrapeptide analogues with low nanomolar potency and high selectivity, derived primarily from the fungus Wardomyces dimerus. Diversification of the cyclic tetrapeptide scaffold via semisynthesis led to the identification of key structural changes that positively impacted the selectivity, potency, and in vitro killing profiles of these compounds. The effectiveness of these compounds as HDAC inhibitors was confirmed through various assays, with different analogues showing reversible or irreversible inhibitory effects against the parasite.
ACS INFECTIOUS DISEASES
(2021)
Correction
Microbiology
Victoria M. Anderson, Karen L. Wendt, Fares Z. Najar, Laura-Isobel McCall, Robert H. Cichewicz
Article
Microbiology
Victoria M. Anderson, Karen L. Wendt, Fares Z. Najar, Laura-Isobel Mccall, Robert H. Cichewicz
Summary: This study proposes a set of tools combining genetic barcoding and metabolomics to help researchers build natural product libraries. Through experimentation with fungi, it was found that a modest number of isolates could provide a significant portion of chemical features, with different subclades containing varying levels of chemical diversity.
Article
Chemistry, Multidisciplinary
Jean A. Bernatchez, Yun-Seo Kil, Elany Barbosa da Silva, Diane Thomas, Laura-Isobel Mccall, Karen L. Wendt, Julia M. Souza, Jasmin Ackermann, James H. McKerrow, Robert H. Cichewicz, Jair L. Siqueira-Neto
Summary: The study identified five leucinostatins (A, B, F, NPDG C, and NPDG D) as potent inhibitors of the intracellular amastigote form of T. cruzi, and leucinostatin B also demonstrated in vivo suppression of T. cruzi in a mouse model of Chagas disease. These findings suggest a potential cross-trypanocidal compound class and provide a platform for further chemical derivatization for the development of effective treatments against T. cruzi.
Article
Plant Sciences
Victoria M. Anderson, Karen L. Wendt, James B. Caughron, Hagan P. Matlock, Nitin Rangu, Fares Z. Najar, Andrew N. Miller, Mark R. Luttenton, Robert H. Cichewicz
Summary: The need for new chemical matter to support the discovery of bioactive compounds has led natural product researchers to explore various source organisms and environments. This study compared fungi from different biomes and found modest differences in physiological performance and chemical output, but no significant differences in chemical richness. Certain fungal genera were more strongly associated with aquatic sediments compared to the surrounding terrestrial environment. These findings suggest that focusing efforts on sampling unique microbial resources in an environment may enhance the diversity of natural products needed for chemical discovery.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Plant Sciences
Sarath P. D. Senadeera, Dongdong Wang, Chang-Kwon Kim, Emily A. Smith, David E. Durrant, Patrick A. Alexander, Karen L. Wendt, Andrew G. Stephen, Deborah K. Morrison, Robert H. Cichewicz, Curtis J. Henrich, John A. Beutler
Summary: Seven new peptaibols were isolated from the fungus Tolypocladium inflatum, which showed inhibitory effects on the interaction between Raf and oncogenic Ras. The structures and activities of the peptaibols were determined using various analytical methods. However, these peptaibols exhibited low selectivity in different cell lines.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Chemistry, Physical
Chance Lander, Vardhan Satalkar, Junjie Yang, Xiaoliang Pan, Zheng Pei, Aayushi Chatterji, Chungen Liu, Kenneth M. Nicholas, Robert H. Cichewicz, Zhibo Yang, Yihan Shao
Summary: We propose a simple procedure for visualizing electron density changes during chemical reactions. By mapping grid points from a stationary structure to distorted positions around atoms of another stationary structure, we can observe the variations in electron density during bond formation and cleavage. The method has been validated for several reactions and demonstrated in the case of copper triflate catalyzed N2O fragmentation.
Article
Chemistry, Organic
Yun-Seo Kil, Jianlan You, Karen L. Wendt, Jarrod B. King, Robert H. Cichewicz
Summary: Fusapyrones are fungal metabolites with broad-spectrum antibacterial and antifungal properties. This study successfully determined the full structures of fusapyrones and reinterpreted the absolute configurations of previously published metabolites using spectroscopic, chemical, and computational techniques. Biological testing demonstrated that fusapyrones inhibit and disrupt biofilm formation by Candida albicans, a human fungal pathoge.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Plant Sciences
Lin Du, Saikat Haldar, Jarrod B. King, Allison O. Mattes, Shikha Srivastava, Karen L. Wendt, Jianlan You, Chad Cunningham, Robert H. Cichewicz
Summary: Fungi pose a persistent threat to humankind as emerging and re-emerging pathogens exhibit resistance to approved antifungals. To address this problem, researchers are exploring endophytic fungi for the discovery of new antifungal natural products, based on their mutualistic relationship with plants and their ability to produce chemical defense measures.
JOURNAL OF NATURAL PRODUCTS
(2023)