Review
Chemistry, Medicinal
Andrea Castaneda, Ricardo Ferraz, Monica Vieira, Isabel Cardoso, Vitor Vasconcelos, Rosario Martins
Summary: Neurodegenerative diseases, particularly dementia like Alzheimer's disease, are significant issues in society due to the aging population. Current pharmaceuticals for AD are only symptomatic and do not halt the progression of the disease. Therefore, research on molecules with therapeutic potential has become a major focus in the scientific community.
Article
Nutrition & Dietetics
Ran Xiao, Rui Liang, Yun-hui Cai, Jie Dong, Lin Zhang
Summary: This study developed an intelligent screening method based on cheminformatics to discover new ingredients for Alzheimer's disease. The research successfully identified a promising compound that showed protective effects on neuronal cells against A beta/Cu2+/AA-induced damage through multiple mechanisms.
FRONTIERS IN NUTRITION
(2022)
Article
Biochemistry & Molecular Biology
Linnea Charlotta Hjelm, Hanna Lindberg, Stefan Stahl, John Lofblom
Summary: Affibody molecules are small affinity proteins with excellent properties. A new type of protein scaffold based on a dimeric form of affibodies has been developed, which has a distinct secondary structure content and mode of binding. The scaffold forms a tunnel-like cavity upon binding, encapsulating the target peptide. Selections from a high-complexity phage-displayed library using this scaffold resulted in the identification of high-affinity binders that effectively inhibit amyloid aggregation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Filippa Lo Cascio, Paola Marzullo, Rakez Kayed, Antonio Palumbo Piccionello
Summary: This review highlights recent research on modifying the structure of curcumin to search for new effective therapeutic agents against neurodegenerative diseases, with a particular focus on Alzheimer's disease.
Article
Biochemistry & Molecular Biology
Blazej Grodner, Mariola Napiorkowska, Dariusz Maciej Pisklak
Summary: This study evaluated the inhibition efficacy of four aminoalkanol derivatives on acetylcholinesterase in vitro. The results showed that the inhibitory potency of the derivatives varied depending on the nature of the substituents, with isopropylamine and/or methyl substituents being the most effective. Docking studies suggested that the compounds bind to the peripheral anionic site rather than entering the catalytic pocket.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Katherine O. Kopp, Margaret E. Greer, Elliot J. Glotfelty, Shih-Chang Hsueh, David Tweedie, Dong Seok Kim, Marcella Reale, Neil Vargesson, Nigel H. Greig
Summary: The immunomodulatory imide drug (IMiD) class, consisting of thalidomide and its derivatives lenalidomide and pomalidomide, has greatly improved the treatment of specific cancers and possesses potent anticancer and anti-inflammatory actions. These actions are mainly mediated by the binding of IMiDs to the human protein cereblon, resulting in the modification of protein degradation and the emergence of new substrate proteins. However, this binding also leads to adverse effects, including teratogenicity.
Review
Biochemistry & Molecular Biology
Flavio A. R. Barbosa, Romulo F. S. Canto, Kerolain F. Teixeira, Anacleto S. de Souza, Aldo S. de Oliveira, Antonio L. Braga
Summary: Alzheimer's disease (AD) is a prevalent type of dementia that affects millions of older people worldwide. Selenium-containing compounds have shown potential as multi-targeted drugs for the treatment of AD due to their antioxidant and anticholinesterase properties. These compounds can decrease the aggregation of amyloid-beta (A beta), a key feature of AD. Some selenium-derived compounds have molecular features similar to FDA-approved drugs, suggesting that they may have optimized pharmacokinetic properties.
CURRENT MEDICINAL CHEMISTRY
(2023)
Review
Geriatrics & Gerontology
Yuqing Liu, Xin Chen, Yutong Che, Hongli Li, Zheyu Zhang, Weijun Peng, Jingjing Yang
Summary: Alzheimer's disease poses a serious threat to the health and safety of the elderly population and is a major public health concern. Long non-coding RNAs (lncRNAs) have been shown to play important roles in AD pathogenesis, providing potential avenues for the discovery of novel therapeutic targets and drugs for the disease.
Review
Pharmacology & Pharmacy
Teresa Pardo-Moreno, Anabel Gonzalez-Acedo, Antonio Rivas-Dominguez, Victoria Garcia-Morales, Francisco Jose Garcia-Cozar, Juan Jose Ramos-Rodriguez, Lucia Melguizo-Rodriguez
Summary: This article discusses the treatment approaches for Alzheimer's disease, including approved drugs, investigational therapies, and alternative methods to improve lifestyle.
Article
Biochemistry & Molecular Biology
Maria Podsiedlik, Magdalena Markowicz-Piasecka, Joanna Sikora
Summary: The aim of this study was to assess the potency of selected antipsychotic drugs on the main pathological hallmarks of Alzheimer's disease. The tested antipsychotics showed inhibition on acetylcholinesterase and Aβ aggregation, and exhibited antioxidant properties in cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Sweta Priyadarshini Pradhan, Pratap Kumar Sahu, Anindita Behera
Summary: Alzheimer's disease (AD) and type-II diabetes mellitus (DM) are mutually related chronic neurodegenerative disorders. Chronic DM increases the risk for AD due to insulin resistance and cognitive dysfunction. Repurposing of antidiabetic drugs and nanotechnological interventions show promise in the prevention and treatment of AD. This review explores the cellular and molecular pathophysiologies of AD and type-II DM, the use of in vivo DM models in AD studies, and the potential of antidiabetic drugs and nanodelivery systems for AD treatment.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Review
Chemistry, Medicinal
Wenbo Ji, Baofeng Gong, Hong Jin, Xiaohan Chen, Peng Li, Wenbin Cheng, Yuchen Zhao, Bin He, Jianhua Zhuang, Jie Gao, You Yin
Summary: Alzheimer's disease is a progressive neurodegenerative disorder characterized by memory loss and social interaction difficulties, currently lacking effective drugs for treatment.
MINI-REVIEWS IN MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Sandipan Chakraborty, Jyotirmoy Rakshit, Jaya Bandyopadhyay, Soumalee Basu
Summary: Through multiple approaches, neohesperidin is found to inhibit both BACE1 and Aβ aggregation, presenting as a potential non-toxic multi-potent scaffold for the development of Alzheimer's disease therapeutics.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Pharmacology & Pharmacy
Mingyao You, Ping Yuan, Liangqian Li, Hongbei Xu
Summary: This research utilized a comprehensive review and network pharmacology to identify the HIF-1 signaling pathway as a potential pathway for Icariin's treatment against Alzheimer's disease (AD).
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Clinical Neurology
Antonio Ancidoni, Ilaria Bacigalupo, Giulia Remoli, Eleonora Lacorte, Paola Piscopo, Giulia Sarti, Massimo Corbo, Nicola Vanacore, Marco Canevelli
Summary: The relationship between cancer and dementia has sparked interest in repurposing anticancer agents for Alzheimer's disease. Clinical trials testing approved anticancer drugs in AD show promise, but published studies on the topic have controversial findings. Larger and high-quality clinical trials are needed to confirm and extend the promising results from preclinical studies.
ALZHEIMERS RESEARCH & THERAPY
(2021)
Article
Multidisciplinary Sciences
Anna Henzi, Adriano Aguzzi
Summary: The study found that PrP is not essential for peripheral nerve repair processes, and Adgrg6 may sustain its function in peripheral nerve repair independently of its activation by PrP.
Article
Genetics & Heredity
Bei Li, Meiling Chen, Adriano Aguzzi, Caihong Zhu
Summary: The study found that while Msr1 expression is upregulated in prion-infected mouse brains, deficiency of Msr1 does not impact disease progression or lesion patterns. This suggests that Msr1 does not play a major role in prion pathogenesis.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2021)
Article
Biochemistry & Molecular Biology
Georg Meisl, Timothy Kurt, Itzel Condado-Morales, Cyrus Bett, Silvia Sorce, Mario Nuvolone, Thomas C. T. Michaels, Daniel Heinzer, Merve Avar, Samuel I. A. Cohen, Simone Hornemann, Adriano Aguzzi, Christopher M. Dobson, Christina J. Sigurdson, Tuomas P. J. Knowles
Summary: Prions, consisting of pathological aggregates of cellular prion protein, have the ability to replicate and cause neurodegenerative diseases. The formation of these aggregates and their rates have been challenging to elucidate in vivo. Using a mathematical framework and microfluidic measurements in mice, the overall aggregation reaction has been dissected into constituent processes and reaction rates quantified. Results show that prion multiplication in vivo is slower than in vitro, but efficient compared with other amyloid systems, displaying scaling behavior characteristic of aggregate fragmentation. This provides a framework for understanding disease-associated aggregation processes within living organisms.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
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)
Article
Clinical Neurology
Christopher J. Love, Daniel Kirschenbaum, Magdy Selim, Eng H. Lo, Elisabeth Rushing, Myron Spector, Adriano Aguzzi
Summary: The study found that chronic hemorrhagic stroke lesions contain abundant collagenous material, primarily consisting of collagen 3. The collagenase rat model successfully reproduced the morphology and composition of chronic human hemorrhagic stroke lesions. By identifying new pathological features of hemorrhagic stroke lesions, these results are important for treatment and recovery strategies.
Article
Medicine, Research & Experimental
Asvin K. K. Lakkaraju, Karl Frontzek, Emina Lemes, Uli Herrmann, Marco Losa, Rajlakshmi Marpakwar, Adriano Aguzzi
Summary: This study found that prion infection and prion-mimetic antibodies deplete PIKfyve, a phosphoinositide kinase controlling endolysosomal maturation, leading to endolysosomal hypertrophy and activation of lysosomal enzymes. This depletion of PIKfyve is mediated by acyltransferases zDHHC9 and zDHHC21, whose topology is disturbed by prion infection, resulting in vacuolation in prion diseases. Restoring PIKfyve levels through different methods can suppress prion-induced vacuolation and restore lysosomal homeostasis.
EMBO MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Laia Lidon, Laura Llao-Hierro, Mario Nuvolone, Adriano Aguzzi, Jesus avila, Isidro Ferrer, Jose Antonio del Rio, Rosalina Gavin
Summary: Through research on AD patient samples and mouse models, it was found that there is a parallel association between PrPC and the 4R isoforms of tau protein. Reducing or eliminating PrPC levels leads to an increase in the balance of tau protein 3R/4R.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Caihong Zhu, Adriano Aguzzi
Summary: Prion diseases are neurodegenerative disorders caused by the abnormal conformational conversion of cellular prion protein. The phenomenon of prion-like spread has also been observed in other disease-associated proteins, such as Aβ, tau, and α-synuclein. Prion protein may play a role in the pathogenesis of a broad spectrum of neurodegenerative conditions, including Alzheimer's and Parkinson's disease.
JOURNAL OF CELL SCIENCE
(2021)
Article
Cell Biology
Eleanna Kara, Alessandro Crimi, Anne Wiedmer, Marc Emmenegger, Claudia Manzoni, Sara Bandres-Ciga, Karishma D'Sa, Regina H. Reynolds, Juan A. Botia, Marco Losa, Veronika Lysenko, Manfredi Carta, Daniel Heinzer, Merve Avar, Andra Chincisan, Cornelis Blauwendraat, Sonia Garcia-Ruiz, Daniel Pease, Lorene Mottier, Alessandra Carrella, Dezirae Beck-Schneider, Andreia D. Magalhaes, Caroline Aemisegger, Alexandre P. A. Theocharides, Zhanyun Fan, Jordan D. Marks, Sarah C. Hopp, Andrey Y. Abramov, Patrick A. Lewis, Mina Ryten, John Hardy, Bradley T. Hyman, Adriano Aguzzi
Summary: Through a genome-wide siRNA screen, researchers identified 38 genes that regulate the cell-to-cell transfer of alpha-synuclein, including the candidate gene ITGA8 identified in a recent PD GWAS. Weighted gene co-expression network analysis and weighted protein-protein network interaction analysis revealed that these genes cluster with known PD genes more frequently than expected by random chance, expanding our understanding of the mechanism of alpha-synuclein spread.
Article
Microbiology
Razieh Kamali-Jamil, Ester Vazquez-Fernandez, Brian Tancowny, Vineet Rathod, Sara Amidian, Xiongyao Wang, Xinli Tang, Andrew Fang, Assunta Senatore, Simone Hornemann, Sandor Dudas, Adriano Aguzzi, Howard S. Young, Holger Wille
Summary: Bovine spongiform encephalopathy (BSE), commonly known as mad cow disease, is a fatal neurodegenerative disease in cattle caused by misfolded PrPSc proteins. This study focused on L-type BSE prions, one of the three prion variants responsible for the disease, and analyzed their structural characteristics using electron microscopy. The results revealed the presence of two classes of amyloid fibrils in L-type BSE prions, with one-protofilament fibrils being more abundant compared to two-protofilament fibrils. Additionally, immunogold labeling confirmed the presence of specific PrP epitopes in the fibrils, supporting the proposed four-rung beta-solenoid model for the infectious PrPSc structure.
Article
Clinical Neurology
Asvin K. K. Lakkaraju, Silvia Sorce, Assunta Senatore, Mario Nuvolone, Jingjing Guo, Petra Schwarz, Rita Moos, Pawel Pelczar, Adriano Aguzzi
Summary: Prion infections cause derangement in glial cells but not in neurons. Expressing PrP(C) selectively in neurons and astrocytes of mice, we found that prion accumulation and disease occurred in neuron-restricted expression, while astrocyte-restricted expression did not lead to clinical disease or inflammation. This suggests a nonautonomous mechanism in which prion-infected neurons instruct astrocytes and microglia to drive neural dysfunction.
Article
Microbiology
Marc Emmenegger, Sreedhar Saseendran F. Kumar, Vishalini J. Emmenegger, Tomas J. Malinauskas, Thomas Buettner, Laura Rose, Peter Schierack, Martin B. Sprinzl, Clemens Sommer, Karl B. Lackner, Adriano Aguzzi, Dirk B. Roggenbuck, Katrin B. M. Frauenknecht
Summary: SARS-CoV-2 infection can lead to diverse symptoms, with some patients developing hypercoagulation and autoantibody responses. Research has shown that infection with SARS-CoV-2 can result in the production of autoantibodies, particularly IgM antibodies targeting coagulation proteins. Further investigation is needed to explore the relationship between SARS-CoV-2 infection, autoantibody production, and disease severity.
Article
Biology
Yingjun Liu, Assunta Senatore, Silvia Sorce, Mario Nuvolone, Jingjing Guo, Zeynep H. Gumus, Adriano Aguzzi
Summary: Cultured brain slices from mice upregulate senescence-associated genes and reproduce transcriptional characteristics of aged brains. Prions accelerate brain aging. This study establishes an innovative model system for studying brain aging.
COMMUNICATIONS BIOLOGY
(2022)
Correction
Biology
Yingjun Liu, Assunta Senatore, Silvia Sorce, Mario Nuvolone, Jingjing Guo, Zeynep H. Gumus, Adriano Aguzzi
COMMUNICATIONS BIOLOGY
(2022)
Article
Clinical Neurology
Regina R. Reimann, Martina Puzio, Antonella Rosati, Marc Emmenegger, Bernard L. Schneider, Pamela Valdes, Danzhi Huang, Amedeo Caflisch, Adriano Aguzzi
Summary: The cellular prion protein PrPC mediates neurotoxicity of prions and protein aggregates, but the mechanisms are not well understood. Antibody-derived ligands against PrPC induce neurotoxicity through hydrogen bonding and suppressing this bond prolongs the lives of prion-infected mice, suggesting convergent pathways. A study found that the toxic effects of these ligands require a specific amino acid residue within PrPC, which could be a potential target for preventing prion-related neurodegeneration.
