Review
Chemistry, Analytical
Arezoo Mirzaie, Hassan Nasrollahpour, Balal Khalilzadeh, Ali Akbar Jamali, Raymond J. Spiteri, Hadi Youse, Ibrahim Isildak, Reza Rahbarghazi
Summary: Alzheimer's disease is a prevalent neurodegenerative disorder characterized by progressive deterioration, loss of neurons, and cognitive decline. Amyloid beta and Tau proteins are key biomarkers of the disease, and their abnormal levels in biofluids, particularly cerebrospinal fluid, are directly linked to the incidence and progression of Alzheimer's. Developing sensitive and reliable methods for screening and evaluating these biomarkers in cerebrospinal fluid can aid in early diagnosis and treatment. This article discusses the impact of Alzheimer's on cerebrospinal fluid and provides an overview of the latest biosensors for detecting amyloid beta and Tau in cerebrospinal fluid samples.
TRAC-TRENDS IN ANALYTICAL CHEMISTRY
(2023)
Article
Neurosciences
Mari Aksnes, Hans Christian D. Aass, Ann Tiiman, Lars Terenius, Nenad Bogdanovi, Vladana Vukojevi, Anne-Brita Knapskog
Summary: In this small pilot study, there was no association between serum nanoplaques and serum cytokines in patients assessed at a memory clinic. This suggests that serum nanoplaque levels cannot be used to differentiate clinical AD patients from non-AD patients in this unselected memory clinic cohort.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Seda Onder, Kevser Biberoglu, Melike Yuksel, Ozden Tacal
Summary: Alzheimer's disease is characterized by amyloid plaques, neurofibrillary tangles, and neuronal loss. Recent studies focus on multi-targeted drug strategies. TBO, a potential candidate, shows promising effects on reducing amyloid levels and decreasing phosphorylated tau.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Biotechnology & Applied Microbiology
Wenjia Lou, Samuel D. Stimple, Alec A. Desai, Emily K. Makowski, Sibel Kalyoncu, Jesper E. Mogensen, Lotte T. Spang, Desiree J. Asgreen, Arne Staby, Karen Duus, Jan Amstrup, Yulei Zhang, Peter M. Tessier
Summary: Biologics such as peptides and proteins have attractive attributes, but are prone to aggregation. By developing conformation-specific antibodies, a sensitive immunoassay for detecting aggregates has been successfully created. These antibodies not only exhibit high conformational specificity, but also cross-react with amyloid fibrils formed by various polypeptides.
BIOTECHNOLOGY AND BIOENGINEERING
(2021)
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
Cell Biology
Kimberly L. L. Fiock, Ryan K. K. Betters, Marco M. M. Hefti
Summary: Tau phosphorylation, aggregation, and toxicity are important in neurodegeneration. Aggregates of tau protein only form amyloids in mixed tauopathies, not pure tauopathies. Thioflavin staining may be useful for differential diagnosis and tau toxicity mechanisms may differ between different tauopathies.
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Romany Abskharon, Michael R. Sawaya, David R. Boyer, Qin Cao, Binh A. Nguyen, Duilio Cascio, David S. Eisenberg
Summary: In this study, the structure of RNA-bound tau protein fibrils was determined using cryo-EM. The findings demonstrate that RNA is necessary for the integrity of the fibrils and reveal a potential mechanism for the nucleating effects of RNA in neurodegenerative diseases. This research provides insight into the formation of protein aggregates in these diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Tatiana P. MacKeigan, Megan L. Morgan, Peter K. Stys
Summary: In this study, an optimized ThS staining protocol was developed for the sensitive detection of beta-amyloids in the widely used 5xFAD Alzheimer's mouse model. The findings demonstrate the efficacy of a controlled ThS staining protocol and highlight the potential use of ThS for the detection of protein misfolding that precedes clinical manifestation of disease.
Article
Neurosciences
Joseph R. Winer, Allison Morehouse, Laura Fenton, Theresa M. Harrison, Lylian Ayangma, Mark Reed, Samika Kumar, Suzanne L. Baker, William J. Jagust, Matthew P. Walker
Summary: This study found that early-stage tau and Aβ deposition in Alzheimer's disease can impact sleep, with tau burden leading to worse objective sleep and Aβ burden associated with decreased self-reported sleep quality. Aβ deposition also predicts a mismatch between objective and subjective sleep evaluation, with individuals underestimating their sleep, which is further linked to worse executive function.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Clinical Neurology
Amelia Strom, Leonardo Iaccarino, Lauren Edwards, Orit H. Lesman-Segev, David N. Soleimani-Meigooni, Julie Pham, Suzanne L. Baker, Susan M. Landau, William J. Jagust, Bruce L. Miller, Howard J. Rosen, Maria Luisa Gorno-Tempini, Gil D. Rabinovici, Renaud La Joie
Summary: Posterior cortical hypometabolism measured with F-18-fluorodeoxyglucose (FDG)-PET is a marker of neurodegeneration in Alzheimer's disease, and it is mainly associated with structural neurodegeneration and tau pathology, rather than amyloid pathology.
Review
Biochemistry & Molecular Biology
Yuanxin Zhao, Buhan Liu, Jian Wang, Long Xu, Sihang Yu, Jiaying Fu, Xiaoyu Yan, Jing Su
Summary: Neuroinflammation mediated by microglia is a common feature in neurodegenerative diseases. The accumulation of Aβ and tau proteins can disrupt the metabolism of microglia, leading to neuroinflammation.
Article
Geriatrics & Gerontology
Sara Lopez-Garcia, Carmen Lage, Ana Pozueta, Maria Garcia-Martinez, Martha Kazimierczak, Andrea Fernandez-Rodriguez, Maria Bravo, Luis Reyes-Gonzalez, Juan Irure, Marcos Lopez-Hoyos, Eloy Rodriguez-Rodriguez, Pascual Sanchez-Juan
Summary: Reduced sleep time is a predictor of higher levels of tau proteins, particularly in APOE ε4 carriers. Total sleep time estimated by actigraphy may serve as an early biomarker of tau pathology.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Valentina Latina, Anna Atlante, Francesca Malerba, Federico La Regina, Bijorn Omar Balzamino, Alessandra Micera, Annabella Pignataro, Egidio Stigliano, Sebastiano Cavallaro, Pietro Calissano, Giuseppina Amadoro
Summary: In addition to deficits in hippocampal-dependent episodic memory, Alzheimer's Disease (AD) is characterized by sensory impairment in visual cognition due to extensive neuropathology in the retina. A monoclonal antibody called 12A12 has been found to specifically neutralize the harmful tau fragments associated with AD without affecting the normal protein. When administered to a mouse model of AD, 12A12 successfully reduces the accumulation of these tau fragments in the brain and retina, improving the associated symptoms. This study also reveals that 12A12 downregulates the expression of proteins involved in the production of amyloid beta, leading to a decrease in its accumulation in both the hippocampus and retina.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Ashvini Keshavan, Josef Pannee, Thomas K. Karikari, Juan Lantero Rodriguez, Nicholas J. Ashton, Jennifer M. Nicholas, David M. Cash, William Coath, Christopher A. Lane, Thomas D. Parker, Kirsty Lu, Sarah M. Buchanan, Sarah E. Keuss, Sarah-Naomi James, Heidi Murray-Smith, Andrew Wong, Anna Barnes, John C. Dickson, Amanda Heslegrave, Erik Portelius, Marcus Richards, Nick C. Fox, Henrik Zetterberg, Kaj Blennow, Jonathan M. Schott
Summary: The study compared three different blood-based techniques for identifying early stage Alzheimer's disease, with mass spectrometry plasma measures performing significantly better than other measures.
Article
Clinical Neurology
Ashvini Keshavan, Josef Pannee, Thomas K. Karikari, Juan Lantero Rodriguez, Nicholas J. Ashton, Jennifer M. Nicholas, David M. Cash, William Coath, Christopher A. Lane, Thomas D. Parker, Kirsty Lu, Sarah M. Buchanan, Sarah E. Keuss, Sarah-Naomi James, Heidi Murray-Smith, Andrew Wong, Anna Barnes, John C. Dickson, Amanda Heslegrave, Erik Portelius, Marcus Richards, Nick C. Fox, Henrik Zetterberg, Kaj Blennow, Jonathan M. Schott
Summary: The study compared three different blood-based techniques to detect amyloid PET positivity in dementia-free individuals, finding that mass spectrometry plasma measures performed significantly better than other measures, with higher sensitivity and specificity for detecting amyloid PET positivity.
Article
Biochemistry & Molecular Biology
Susanna Navarro, Salvador Ventura
Summary: Protein aggregation is associated with diseases and industrial production. This article reviews computational tools for predicting and identifying protein aggregation.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Chemistry, Medicinal
Anna Sampietro, F. Javier Perez-Areales, Paula Martinez, Elsa M. Arce, Carles Galdeano, Diego Munoz-Torrero
Summary: Research on multitarget anti-Alzheimer agents has seen a rapid increase in publications, with China, Italy, and Spain being the leading countries in this field. The scopolamine-induced amnesia mouse model is commonly used in in vivo studies, and there are variations in research trends among different countries.
Article
Biochemistry & Molecular Biology
Carlos Pintado-Grima, Oriol Barcenas, Salvador Ventura
Summary: This study conducted a large-scale in-silico analysis of the effect of solution pH on the solubility and disorder of intrinsically disordered regions (IDRs) involved in liquid-liquid phase separation (LLPS). The results showed that LLPS-DRs have maximum solubility around physiological pH, where LLPS often occurs, and significant differences were found between proteins that can phase-separate by themselves or those that require a partner.
Article
Biochemistry & Molecular Biology
Carlos Pintado-Grima, Oriol Barcenas, Zoe Manglano-Artunedo, Rita Vilaca, Sandra Macedo-Ribeiro, Irantzu Pallares, Jaime Santos, Salvador Ventura
Summary: Proteome-wide analyses have revealed that amyloidogenic regions are present in most globular proteins, while being underrepresented in intrinsically disordered proteins (IDPs). However, recent research has shown that intrinsically disordered regions (IDRs) do contain significant amyloid load in the form of cryptic amyloidogenic regions (CARs), which are exposed to solvent and are more polar than conventional amyloid regions. CARs are associated with both IDPs function and malfunction, and their presence is linked to pathologies such as cancer and Alzheimer's disease. To explore these previously unnoticed amyloidogenic regions, CARs-DB, a database containing precomputed predictions for all CARs in the IDPs deposited in the DisProt database, was developed. CARs-DB allows for easy access to a large number of unique CARs and has been validated by demonstrating the amyloidogenic potential of selected CARs.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Chemistry, Medicinal
Julia Jarne-Ferrer, Christian Grinan-Ferre, Aina Bellver-Sanchis, Santiago Vazquez, Diego Munoz-Torrero, Merce Pallas
Summary: Alzheimer's disease is a progressive neurological disorder with limited treatment options. However, this study suggests that chronic low-dose co-treatment with sEH and AChE inhibitors may have neuroprotective effects and improve cognition in mouse models.
Article
Chemistry, Medicinal
Diego Munoz-Torrero, Lawrence M. Schopfer, Oksana Lockridge
Summary: Chronic low-dose exposure to organophosphorus toxicants is associated with increased risk of impaired cognition and neurodegenerative diseases. The formation of organophosphate-induced high-molecular-weight protein aggregates that disrupt cell function may be the mechanism explaining this relationship.
CHEMICAL RESEARCH IN TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Kamila Czarnecka, Malgorzata Girek, Pawel Krecisz, Robert Skibinski, Kamil Latka, Jakub Jonczyk, Marek Bajda, Piotr Szymczyk, Grzegorz Galita, Jacek Kabzinski, Ireneusz Majsterek, Alba Espargaro, Raimon Sabate, Pawel Szymanski
Summary: Alzheimer's disease (AD) is a progressive neurodegenerative brain disease and current drugs are not entirely effective in its treatment. This study evaluated eight derivatives as candidates for stronger anti-AD potential with fewer side effects. Compound 3e displayed moderate inhibition of cholinesterase and significant inhibition of A beta aggregation, indicating promise as a potential new anti-AD drug.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Javier Garcia-Pardo, Andrea Bartolome-Nafria, Antonio Chaves-Sanjuan, Marcos Gil-Garcia, Cristina Visentin, Martino Bolognesi, Stefano Ricagno, Salvador Ventura
Summary: The study reports the cryo-electron microscopy structure of hnRNPDL-2 fibrils, revealing its stable, non-toxic, and nucleic acid-binding properties. The structure provides insights into the mechanism of hnRNPDL-2 fibrillation and its association with LGMD D3. Additionally, the study highlights how alternative splicing controls the assembly of different hnRNPDL isoforms, generating functional diversity.
NATURE COMMUNICATIONS
(2023)
Article
Nanoscience & Nanotechnology
Molood Behbahanipour, Roger Benoit, Susanna Navarro, Salvador Ventura
Summary: A novel nanoparticle has been developed that can neutralize SARS-CoV-2 virus. The nanoparticle is biocompatible and stable, and shows potential for therapeutic and diagnostic applications.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Chemistry, Multidisciplinary
Susanna Navarro, Marta Diaz-Caballero, Francesca Peccati, Lorena Roldan-Martin, Mariona Sodupe, Salvador Ventura
Summary: Enzymes fold into specific 3D protein structures and exhibit high catalytic efficiency and selectivity. Artificial amyloids have been shown to have catalytic activity and advantages over natural enzymes. A recent study found that short peptides can self-assemble into amyloid fibrils with catalytic activity by coordinating and retaining different divalent metal cations. These findings provide new insights into the design of artificial metalloenzymes and support the role of amyloid-like structures in the origin of life.
News Item
Biochemistry & Molecular Biology
Javier Garcia-Pardo, Salvador Ventura
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Aleksandra E. Badaczewska-Dawid, Aleksander Kuriata, Carlos Pintado-Grima, Javier Garcia-Pardo, Michal Burdukiewicz, Valentin Iglesias, Sebastian Kmiecik, Salvador Ventura
Summary: Protein aggregation is associated with aging and different pathologies, and is a challenge in the industrial production of biotherapeutics. Previous research in model organisms has provided insights into the biophysical principles of this process and led to the development of computational tools. A3D-MODB is a comprehensive database that allows for the study of protein aggregation in 12 model species and provides additional information for better understanding protein aggregation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Medicine, General & Internal
Joanna Kowalczyk, Krystyna Skalicka-Wozniak, Barbara Budzynska, Nesrine El Sayed, Alba Espargaro, Raimon Sabate
Summary: In preclinical studies, simple coumarins and furanocoumarins have been found to have procognitive abilities and exhibit antioxidative, anti-inflammatory, and inhibitory effects on acetylcholinesterase activities. However, little is known about their impact on amyloidal structure formation, the leading cause of Alzheimer's disease. Limettin showed the strongest inhibitory profile on A beta 40 aggregation, but all tested compounds had minimal influence on A beta 42 and tau protein aggregation. Although the research is still in its preliminary stage, the findings suggest that coumarins may serve as potential multitarget agents for AD treatment.
CURRENT ISSUES IN PHARMACY AND MEDICAL SCIENCES
(2022)