Article
Multidisciplinary Sciences
Kevin A. Murray, Carolyn J. Hu, Sarah L. Griner, Hope Pan, Jeannette T. Bowler, Romany Abskharon, Gregory M. Rosenberg, Xinyi Cheng, Paul M. Seidler, David S. Eisenberg
Summary: Neurodegenerative diseases are characterized by the accumulation of aggregated proteins, and inhibiting the formation of these aggregates is a potential therapeutic strategy. Using de novo protein design, researchers have developed a library of mini-protein inhibitors that specifically target the amyloid structures of tau, Aβ, and α Syn. These inhibitors show promising results in preventing aggregation and rescuing motor deficits in animal models of PD and AD.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Aiko Robert, Michael Scholl, Thomas Vogels
Summary: Recent research has shown that injecting purified tau aggregates from human tauopathy patients can replicate the structural features and cell type specificity of the original tau pathology. These models may have unique translational value in studying the functional consequences of tau pathology, tau-based diagnostics, and tau-targeting therapeutics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Narendran Annadurai, Jiri Hruby, Agata Kubickova, Lukas Malina, Marian Hajduch, Viswanath Das
Summary: Tauopathies are neurodegenerative diseases categorized into three types based on tau isoforms. Differences in seeding propensities and induction of tau aggregation were observed between R2 and R3 aggregates. The accumulation of pSer262 tau was visible earlier in cells induced with R2 aggregates, suggesting a role for the R2 region in disease progression and neuropathology of 4R tauopathies.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Romany Abskharon, Hope Pan, Michael R. Sawaya, Paul M. Seidler, Eileen J. Olivares, Yu Chen, Kevin A. Murray, Jeffrey Zhang, Carter Lantz, Megan Bentzel, David R. Boyer, Duilio Cascio, Binh A. Nguyen, Ke Hou, Xinyi Cheng, Els Pardon, Christopher K. Williams, Alissa L. Nana, Harry V. Vinters, Salvatore Spina, Lea T. Grinberg, William W. Seeley, Jan Steyaert, Charles G. Glabe, Rachel R. Ogorzalek Loo, Joseph A. Loo, David S. Eisenberg
Summary: This study presents a novel approach for the design of antibody therapies for Alzheimer's disease, addressing challenges such as poor efficacy and blood-brain barrier penetration. By grafting specific sequences onto a camel heavy chain antibody scaffold, researchers were able to create nanobodies that block tau aggregation and improve BBB penetration. These synthetic antibodies may hold promise for inhibiting the prion-like spreading of tau and other proteins implicated in AD.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Physical
Takahiro Takekiyo, Natsuki Yamada, Taku Amo, Chikako T. Nakazawa, Atushi Asano, Tohru Ichimura, Minoru Kato, Yukihiro Yoshimura
Summary: The development of standard dissolution agents for amyloid aggregates is crucial for understanding treatment strategies and improving protein recovery. However, there are currently no standard dissolution agents for many amyloid aggregates. In this study, the dissolution ability of alkali halides on α-synuclein amyloid aggregates formed under mild conditions was investigated.
JOURNAL OF MOLECULAR LIQUIDS
(2023)
Article
Biochemistry & Molecular Biology
Narendran Annadurai, Lukas Malina, Mario Salmona, Luisa Diomede, Antonio Bastone, Alfredo Cagnotto, Margherita Romeo, Martin Srejber, Karel Berka, Michal Otyepka, Marian Hajduch, Viswanath Das
Summary: Experimental evidence suggests that tau pathology spreads in a prion-like manner in Alzheimer's disease, with tau seeding detected early in human AD brains. Antitumour drugs have been found to protect against neurodegeneration, potentially offering a repurposed therapy for AD. Drugs targeting specific regions of tau can prevent the generation of seed-competent aggregates, reducing tau seeding and toxicity in cells and worms.
Article
Neurosciences
Alejandro Ruiz-Riquelme, Alison Mao, Marim M. Barghash, Heather H. C. Lau, Erica Stuart, Gabor G. Kovacs, K. Peter R. Nilsson, Paul E. Fraser, Gerold Schmitt-Ulms, Joel C. Watts
Summary: Aggregates containing longer Aβ C-terminal variants are more potent inducers of cerebral Aβ deposition. Aβ43 seeds may play a crucial role in the initial stages of Aβ pathology in AD.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Clinical Neurology
TXiaohang Li, Simona Ospitalieri, Tessa Robberechts, Linda Hofmann, Christina Schmid, Ajeet Rijal Upadhaya, Marta J. Koper, Christine A. F. von Arnim, Sathish Kumar, Michael Willem, Kathrin Gnoth, Meine Ramakers, Joost Schymkowitz, Frederic Rousseau, Jochen Walter, Alicja Ronisz, Karthikeyan Balakrishnan, Dietmar Rudolf Thal
Summary: Alzheimer's disease is characterized by the deposition of amyloid beta-peptide (A beta) as plaques, which initially occurs in the neocortex and spreads to other brain regions. The propagation of A beta plaques is led by non-modified A beta followed by aggregate maturation. Different forms of A beta can trigger the propagation/maturation process of A beta aggregates.
Article
Biochemistry & Molecular Biology
Kamlesh M. Makwana, Matthew P. Sarnowski, Jiayuan Miao, Yu-Shan Lin, Juan R. Del Valle
Summary: The study introduces a minimalist approach to mimic the aggregation-prone modules within tau, showing efficacy in inhibiting tau fibril formation through a series of experiments.
ACS CHEMICAL NEUROSCIENCE
(2021)
Review
Neurosciences
Urmi Sengupta, Rakez Kayed
Summary: This review summarizes the histopathological features of specific protein aggregation in several neurodegenerative diseases and discusses their overlap. It also highlights the synergistic interplay among Aβ, tau, and alpha-Syn in these diseases, suggesting a protein triumvirate.
PROGRESS IN NEUROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Galina Limorenko, Meltem Tatli, Rajasekhar Kolla, Sergey Nazarov, Marie-Theres Weil, David C. Schondorf, Daniela Geist, Peter Reinhardt, Dagmar E. Ehrnhoefer, Henning Stahlberg, Laura Gasparini, Hilal A. Lashuel
Summary: The authors present a method to produce co-factor-free fibrils from all full-length Tau isoforms, which allows for the reconstitution of pathology resembling Tau fibrils and the screening of Tau aggregation-modifying compounds for targeted therapies and PET tracers.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Alberto Carpinteiro Soares, Andreia Ferreira, Jonas Marieen, Charlotte Delay, Edward Lee, John Q. Trojanowski, Dieder Moechars, Wim Annaert, Louis De Muynck
Summary: Research shows that key factors such as dynamin-1, actin, and Rac1 play important roles in the neuronal uptake of tau seeds through specific endosomal pathways. In addition, inhibition of the downstream protein PIKfyve can reduce the trafficking of tau seeds into lysosomes and the induction of tau aggregation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Linda Lantz, Hamid Shirani, Bernardino Ghetti, Ruben Vidal, Therese Klingstedt, K. Peter R. Nilsson
Summary: The aggregation and accumulation of brain proteins are characteristic of devastating neurodegenerative diseases. Fluorescent ligands that bind to these accumulations are crucial for characterizing these neuropathological lesions. Donor-acceptor-donor (D-A-D) thiophene-based ligands with different emission properties were synthesized and showed selectivity towards distinct disease-associated protein deposits in postmortem brain tissue from individuals with Alzheimer's disease (AD). By combining D-A-D ligands with conventional thiophene-based ligands, superior spectral separation of distinct protein aggregates in AD tissue sections was achieved. This research provides a basis for developing new fluorescent ligands that can distinguish between aggregated protein species and offers novel strategies for multiplex fluorescence detection of protein aggregates in tissue sections.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Clinical Neurology
Hee Yang Lee, Soljee Yoon, Jeong Hwa Lee, Keunwan Park, Youngeun Jung, Illhwan Cho, Donghee Lee, Jisu Shin, Kyeonghwan Kim, Sunmi Kim, Jimin Kim, Koeun Kim, Seung Hoon Han, Seong Muk Kim, Hye Ju Kim, Hye Yun Kim, Ikyon Kim, Young Soo Kim
Summary: The study identified YIAD002 as a potent dissociator of Aβ aggregates, showing significant reduction in amyloid burden, improved cognitive performance, and alleviated major pathological hallmarks of AD. Mechanism studies suggest that YIAD002 interferes with intermolecular beta-sheet fibrillation by directly interacting with specific domains of Aβ.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Article
Chemistry, Physical
Miaomiao Liu, Wenjuan Wang, Xiuping Hao, Xiaoyan Dong
Summary: Alzheimer's disease and type 2 diabetes mellitus show extensive correlation through cross-aggregation between related pathogenic peptides. This study investigates the cross-amyloid aggregation process of amyloid beta protein (A beta) and human islet amyloid polypeptide (hIAPP). The presence of seeds significantly changes the aggregation pathway, forming heterogeneous aggregates with increased cytotoxicity. Both solution and solid surface results demonstrate that seeds can induce rapid aggregation and promote the aggregation of heterogeneous monomers.
ACTA PHYSICO-CHIMICA SINICA
(2022)
Article
Biochemistry & Molecular Biology
Leah N. Makley, Oleta T. Johnson, Phani Ghanakota, Jennifer N. Rauch, Delaney Osborn, Taia S. Wu, Tomasz Cierpicki, Heather A. Carlson, Jason E. Gestwicki
Summary: Researchers identified potential binding sites in Hsp27 through techniques such as mixed solvent molecular dynamics and NMR solvent mapping, and conducted a fragment-based drug discovery screen. Ultimately, two promising fragments were found, with one fragment significantly increasing affinity under medicinal chemistry intervention while maintaining good ligand efficiency. Additionally, binding to this site partially restored stability of disease-associated Hsp27 variants.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Microbiology
Jennifer N. Rauch, Eric Valois, Sabrina C. Solley, Friederike Braig, Ryan S. Lach, Morgane Audouard, Jose Carlos Ponce-Rojas, Michael S. Costello, Naomi J. Baxter, Kenneth S. Kosik, Carolina Arias, Diego Acosta-Alvear, Maxwell Z. Wilson
Summary: The COVID-19 pandemic has created a massive demand for tools to detect the virus’s genetic material. CREST is a new pipeline that combines common biochemical methods with low-cost instrumentation, providing a solution without sacrificing detection sensitivity.
JOURNAL OF CLINICAL MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yanxian Lin, Yann Fichou, Andrew P. Longhini, Luana C. Llanes, Pengyi Yin, Guillermo C. Bazan, Kenneth S. Kosik, Songi Han
Summary: The liquid-liquid phase separation of tau protein can facilitate amyloid aggregation in some cases, while being independent of aggregation in others. The nature of the interaction driving tau condensation is a differentiating factor between aggregation-prone and aggregation-independent liquid-liquid phase separations.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Physics, Multidisciplinary
Giorgio Schiro, Yann Fichou, Alex P. S. Brogan, Richard Sessions, Wiebke Lohstroh, Michaela Zamponi, Gerald J. Schneider, Francois-Xavier Gallat, Alessandro Paciaroni, Douglas J. Tobias, Adam Perriman, Martin Weik
Summary: The study revealed that solvent-free protein-polymer hybrids can replace hydration water, preserving protein structure and function, with dynamics similar to water's.
PHYSICAL REVIEW LETTERS
(2021)
Article
Medicine, General & Internal
Jennifer N. Rauch, Eric Valois, Jose Carlos Ponce-Rojas, Zach Aralis, Ryan S. Lach, Francesca Zappa, Morgane Audouard, Sabrina C. Solley, Chinmay Vaidya, Michael Costello, Holly Smith, Ali Javanbakht, Betsy Malear, Laura Polito, Stewart Comer, Katherine Arn, Kenneth S. Kosik, Diego Acosta-Alvear, Maxwell Z. Wilson, Lynn Fitzgibbons, Carolina Arias
Summary: This study investigated the prevalence of SARS-CoV-2 in asymptomatic participants in a university community using a CRISPR-based test. The results showed 8 positive cases among students, highlighting the potential of covert viral transmission and the effectiveness of CRISPR-based assays in capturing positive cases in this population.
Article
Chemistry, Physical
Madhur Srivastava, Boris Dzikovski, Jack H. Freed
Summary: The study introduces a wavelet transform-based approach to effectively remove noise from spectroscopic data, demonstrating its ability to accurately extract signals from various types of spectra. By improving the signal-to-noise ratio, it can accurately recover weak signals from complex spectra.
JOURNAL OF PHYSICAL CHEMISTRY A
(2021)
Article
Multidisciplinary Sciences
Kevin Pounot, Markus Appel, Christian Beck, Martin Weik, Giorgio Schiro, Yann Fichou, Tilo Seydel, Frank Schreiber
Summary: Neutron scattering is a nondestructive method for probing the dynamics within samples. This paper presents the workflow and data analysis procedure for investigating protein and hydration water dynamics using neutron backscattering spectroscopy. Two case studies on amyloid proteins are presented to illustrate the method's capability. The importance of neutron scattering in studying dynamics in comparison to other biophysical methods is also discussed.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Article
Chemistry, Inorganic & Nuclear
Aritro Sinha Roy, Madhur Srivastava
Summary: This article presents a wavelet transform technique for resolving simulated and experimental continuous-wave electron spin resonance spectra by separating hyperfine and super-hyperfine components. By analyzing the spectrum and its varying frequency simultaneously, this method exploits the multiresolution property of wavelet transforms to separate distinct features of the spectrum.
Article
Chemistry, Physical
David Talaga, Gary S. Cooney, Vicky Ury-Thiery, Yann Fichou, Yuhan Huang, Sophie Lecomte, Sebastien Bonhommeau
Summary: Total internal reflection tip-enhanced Raman spectroscopy (TIR-TERS) is a promising technique for noninvasive nanoscale chemical characterization of biomolecules. The TERS enhancement achieved in this configuration is significantly higher than that in traditional illumination geometry. TIR-TERS is applied to the study of Tau amyloid fibrils, revealing spectral signatures and structural information of the fibrils.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Chemistry, Physical
Zhikai Zeng, Yann Fichou, Michael Vigers, Karen Tsay, Songi Han
Summary: The aggregation of tau protein is crucial for tauopathies, and cryogenic electron microscopy has provided high-resolution images of pathological tau tangles. Seeded aggregation is believed to play a significant role in the structural propagation of tau fibrils, but direct measurement of structural evolution is currently lacking. Double electron-electron resonance (DEER) holds unique potential to track the structural changes of tau during aggregation and elucidate disease-specific tau aggregation pathways.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Chemistry, Physical
Aritro Sinha Roy, Madhur Srivastava
Summary: Analysis of small molecules is crucial in various fields, but current challenges hinder accurate identification of individual molecules in mixtures. This study presents a novel NMR spectroscopy method that enables reliable analysis of small molecule mixtures.
JOURNAL OF PHYSICAL CHEMISTRY A
(2022)
Article
Biochemistry & Molecular Biology
Aritro Sinha Roy, Madhur Srivastava
Summary: Resolving small molecule mixtures by NMR spectroscopy has been a long-term interest due to its precision, reproducibility, and efficiency. Existing methods have limited applicability, but we developed a scheme using the wavelet packet transform (WPT) technique to generate highly resolved NMR spectra and predict molecular compositions. The method was tested on a dataset of 1000 molecular mixtures with varying compositions, achieving a high true positive rate and low false positive rate. This approach can be easily scaled for larger datasets.
Article
Chemistry, Inorganic & Nuclear
Aritro Sinha Roy, Boris Dzikovski, Dependu Dolui, Olga Makhlynets, Arnab Dutta, Madhur Srivastava
Summary: Accurate analysis of cw ESR spectra is crucial for understanding the structure-function relationships and electrochemical properties of biological or organic free radicals and paramagnetic metal complexes. Current simulation-based methods often fail to accurately extract spectral information due to sensitivity to resolution, artifacts, input parameters, and complexity. We introduce a simulation-independent approach using wavelet packet transform to directly extract g values and hyperfine constants from cw ESR spectra, overcoming challenges associated with poorly resolved and unresolved spectra. The method is demonstrated to be accurate and consistent using experimental spectra of organic radicals and copper-nitrogen complexes, even for minor components with a relative concentration of 5%.
Article
Chemistry, Physical
Gyana Ranjan Sahoo, Aritro Sinha Roy, Madhur Srivastava
Summary: Two-dimensional electron spin resonance (2D ESR) spectroscopy is a unique experimental technique for studying protein structure and dynamics. This study proposes a time-frequency analysis method that resolves the limitation of traditional methods in resolving overlapping peaks in 2D ESR by decomposing the signal and identifying frequency peaks.
JOURNAL OF PHYSICAL CHEMISTRY A
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Jennifer Rauch