Article
Neurosciences
Youssra K. K. Al-Hilaly, Connor Hurt, Janet E. E. Rickard, Charles R. R. Harrington, John M. D. Storey, Claude M. M. Wischik, Louise C. C. Serpell, Ansgar B. B. Siemer
Summary: Aggregation of the tau protein into fibrillar cross-beta aggregates is a characteristic of neurodegenerative diseases like Alzheimer's disease. A recent study found that a tau fragment called dGAE can form filaments in vitro, providing a promising model for studying AD tau filaments. Solid-state NMR was used to characterize the tau filaments and it was found that filaments assembled under non-reducing conditions are more dynamic and less ordered than those assembled in the presence of a reducing agent.
FRONTIERS IN NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Patrick C. A. van der Wel
Summary: Solid-state NMR spectroscopy provides valuable high-resolution structural information primarily focused on inter-atomic distance measurements. This review examines the utility of measuring angular constraints as a complement to distance-based structure determination, focusing on the judicious recoupling of multiple anisotropic ssNMR parameters.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Multidisciplinary Sciences
Ujjayini Ghosh, Wai-Ming Yau, John Collinge, Robert Tycko
Summary: This study investigated the molecular structures of Aβ fibrils in brain tissue of nondemented elderly individuals and AD patients using solid-state NMR, revealing that similar sets of fibril polymorphs develop in both groups but with different relative populations on average. The differences in solid-state NMR data were more significant for Aβ42 fibrils compared to Aβ40 fibrils.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Multidisciplinary
Evelyn Rose Kamski-Hennekam, Jinfeng Huang, Rashik Ahmed, Giuseppe Melacini
Summary: The ability of ATP to modulate protein solubility is critical in understanding proteinopathies like Parkinson's disease. ATP levels decline with age, which is the most significant risk factor for Parkinson's. This study shows that ATP affects multiple stages of alpha-synuclein aggregation, and the disruption of ATP's function may play a role in Parkinson's etiology.
Article
Multidisciplinary Sciences
Guilherme G. Moreira, Francois-Xavier Cantrelle, Andrea Quezada, Filipa S. Carvalho, Joana S. Cristovao, Urmi Sengupta, Nicha Puangmalai, Ana P. Carapeto, Mario S. Rodrigues, Isabel Cardoso, Guenter Fritz, Federico Herrera, Rakez Kayed, Isabelle Landrieu, Claudio M. Gomes
Summary: The study demonstrates that S100B protein acts as an extracellular chaperone for Tau, inhibiting its aggregation and providing evidence for neuro-protective functions.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Nilamuni H. de Silva, Anthony Dahdah, Ewan W. Blanch, Helmut M. Huegel, Subashani Maniam
Summary: In this study, a microwave-assisted, one-pot, three-component, 1,3-dipolar cycloaddition reaction was developed to synthesize bis-spirooxindoles. These compounds showed high regioselectivity and stereoselectivity and demonstrated potential as inhibitors against amyloid-beta fibrillation, making them attractive therapeutic leads for Alzheimer's disease treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Han Na Lee, Mi Suk Jeong, Se Bok Jang
Summary: Amyloid precursor protein (APP) and its homologs play important roles in the nervous system and are overexpressed in cancer cells. Research indicates their involvement in several cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Sandra Schilling, Ajay Pradhan, Amelie Heesch, Andrea Helbig, Kaj Blennow, Christian Koch, Lea Bertgen, Edward H. Koo, Gunnar Brinkmalm, Henrik Zetterberg, Stefan Kins, Simone Eggert
Summary: This study compares the effects of different APP genetic mutations on their processing and pathogenic mechanisms in Alzheimer's disease. The results show significant differences in the underlying mechanisms for familial AD mutations located at the alpha-, beta-, and gamma-secretase cleavage sites. Different mutations have different effects on APP processing and the generation of A β peptides.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Review
Chemistry, Multidisciplinary
Wing Ying Chow, Gaël De Paepe, Sabine Hediger
Summary: Solid-state NMR spectroscopy with magic-angle spinning enables the investigation of biological systems in their native context. However, low sensitivity due to the presence of other molecular species and the challenge of detecting low concentration species limit the feasibility of certain investigations. By applying dynamic nuclear polarization (DNP), the experimental time required can be significantly reduced, broadening the scope of biological solid-state NMR applications.
Article
Biochemistry & Molecular Biology
Leela Paladugu, Abeer Gharaibeh, Nivya Kolli, Cameron Learman, Tia C. Hall, Lixin Li, Julien Rossignol, Panchanan Maiti, Gary L. Dunbar
Summary: Recent studies suggest that the anti-diabetic drug liraglutide can reduce neuroinflammatory responses in the early stages of Alzheimer's disease before significant cognitive changes are observed, indicating its potential as a neuroprotective and anti-inflammatory therapy in prodromal stages of AD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Physical
Monu Kaushik, Hugo Lingua, Gabriele Stevanato, Margarita Elokova, Moreno Lelli, Anne Lesage, Olivier Ouari
Summary: This study introduces trehalose-based DNP polarizing matrices optimized for experiments at low temperatures and explores the efficiency of various formulation protocols. The results show that these new polarizing media outperform the conventionally used water/glycerol mixture at higher temperatures, providing new possibilities for DNP enhanced solid-state NMR spectroscopy close to ambient temperature.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Chemistry, Multidisciplinary
Yijing Tang, Dong Zhang, Xiong Gong, Jie Zheng
Summary: This study demonstrates a rational design strategy of an amyloid-aggregation-induced emission (AIE)-active molecule, G7-TBA, which serves as a multiple-target, dual-function amyloid probe and modulator for detecting, monitoring, and altering amyloid aggregation of different amyloid proteins.
ADVANCED FUNCTIONAL MATERIALS
(2022)
Article
Chemistry, Multidisciplinary
Andrei A. Kuzhelev, Vasyl Denysenkov, Iram M. Ahmad, Olga Yu. Rogozhnikova, Dmitry Trukhin, Elena G. Bagryanskaya, Victor M. Tormyshev, Snorri Th. Sigurdsson, Thomas F. Prisner
Summary: Dynamic nuclear polarization (DNP) is an effective method for enhancing the sensitivity of nuclear magnetic resonance (NMR) experiments. This study demonstrates that DNP can achieve over 50 times enhancement in viscous liquids using narrow-line polarizing agents and a microwave/RF double-resonance probehead. The results show potential applications of this new DNP approach for chemistry and biology, as demonstrated by the hyperpolarized 1H NMR spectra of tripeptides, triglycine, and glypromate in glycerol-d8.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Heidi R. R. Wassef, Patrick M. M. Colletti
Summary: Hoilund-Carlsen and colleagues express concerns about the reliability of amyloid PET for excluding Alzheimer's disease. We provide additional studies on amyloid PET and discuss the diagnostic challenges in Alzheimer's disease. We also discuss the limitations of amyloid in the diagnosis and evaluation of therapy response in AD.
CLINICAL NUCLEAR MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Md. Ataur Rahman, Md Saidur Rahman, MD. Hasanur Rahman, Mohammad Rasheduzzaman, A. N. M. Mamun-Or-Rashid, Md Jamal Uddin, Md Rezanur Rahman, Hongik Hwang, Myung-Geol Pang, Hyewhon Rhim
Summary: Alzheimer's disease is characterized by the formation of intracellular tau protein aggregates and extracellular amyloid-beta plaques, with dysregulation of autophagy playing a critical role in AD pathogenesis. Modulation of autophagy has been identified as a promising approach to treating AD by facilitating the removal of toxic protein aggregates. Atg genes and APP are thought to influence the development of AD, establishing a bidirectional link between autophagy and AD pathology.