Article
Geriatrics & Gerontology
Karina Cuanalo-Contreras, Jonathan Schulz, Abhisek Mukherjee, Kyung-Won Park, Enrique Armijo, Claudio Soto
Summary: Accumulation of misfolded protein aggregates is a common event in age-related protein misfolding disorders, and our study shows that this accumulation is significantly increased in aging. Proteins in aged samples have a higher amount of insoluble aggregates compared to young samples, suggesting a role for protein misfolding and aggregation in aging.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Article
Neurosciences
Johan N. K. Larsson, Sofie Nystroem, Per Hammarstrom
Summary: Neurodegenerative diseases are associated with the accumulation of misfolded proteins. HSP10, a molecular chaperone, plays an important role in protein homeostasis in these diseases by influencing fibril formation and structure.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Marco Persico, Sara Garcia-Vinuales, Anna Maria Santoro, Valeria Lanza, Grazia Raffaella Tundo, Diego Sbardella, Massimiliano Coletta, Valeria Romanucci, Armando Zarrelli, Giovanni Di Fabio, Caterina Fattorusso, Danilo Milardi
Summary: This study analyzed the proteasome-enhancing abilities of two natural diastereoisomers, Sil A and Sil B, belonging to the family of flavonolignans. The results showed that Sil B is more efficient in enhancing the activity of yeast 20S proteasome, while Sil A has a higher affinity and more efficient activation for human 20S proteasome. Experimental and computational studies revealed the crucial role played by stereospecific interactions in driving the binding of these diastereoisomers to the 20S proteasome, providing insights for future rational design of proteasome enhancers.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Neurosciences
Jessica A. Lawrence, Patricia Aguilar-Calvo, Daniel Ojeda-Juarez, Helen Khuu, Katrin Soldau, Donald P. Pizzo, Jin Wang, Adela Malik, Timothy F. Shay, Erin E. Sullivan, Brent Aulston, Seung Min Song, Julia A. Callender, Henry Sanchez, Michael D. Geschwind, Subhojit Roy, Robert A. Rissman, JoAnn Trejo, Nobuyuki Tanaka, Chengbiao Wu, Xu Chen, Gentry N. Patrick, Christina J. Sigurdson
Summary: Endolysosomal defects, including the reduction of Hrs and STAM1, exacerbate synaptic derangements and accelerate neurodegeneration in prion-infected brains. Depletion of neuronal Hrs leads to increased surface levels of PrPC, contributing to the rapidly advancing disease through neurotoxic signaling. The findings highlight the importance of proteostatic pathways and synaptic integrity in prion diseases.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Alexander G. Bobylev, Roman S. Fadeev, Liya G. Bobyleva, Margarita I. Kobyakova, Yuri M. Shlyapnikov, Daniil V. Popov, Ivan M. Vikhlyantsev
Summary: The study found that amyloid aggregates of smooth-muscle titin can impair cell adhesion and lead to cell death. The surface roughness may be a key factor contributing to the highly antiadhesive properties. The negative impact of amyloid aggregates on cell adhesion is likely intrinsic to other amyloid proteins with similar structure and properties.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Analytical
Li-En Lin, Kun Miao, Chenxi Qian, Lu Wei
Summary: Amyloid aggregation, a pathological hallmark in neurodegenerative diseases, was studied using label-free high-resolution imaging and machine learning for specific segmentation of aggregate cores and peripheral filaments. This non-invasive imaging technology allows precise and multiplex high-resolution imaging of protein aggregates and their micro-environment, opening up new biomedical applications.
Review
Cell Biology
Mario Gonzalez-Garcia, Giuliana Fusco, Alfonso De Simone
Summary: The conversion of soluble proteins into insoluble amyloid aggregates is linked to various neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. The small prefibrillar oligomers formed during protein aggregation are identified as the most harmful species. Interactions with biological membranes play a crucial role in the onset of cellular toxicity. Further research is needed to understand the transient interactions involving heterogeneous protein aggregates for developing effective therapeutic strategies against protein misfolding diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Chemistry, Analytical
Yu P. Zhang, Evgeniia Lobanova, Derya Emin, Sergey V. Lobanov, Antonina Kouli, Caroline H. Williams-Gray, David Klenerman
Summary: This study introduces a new method for the diagnosis of early Parkinson's disease. The results show that the proportion of soluble alpha-synuclein aggregates can distinguish between Parkinson's disease patients and control groups, with Parkinson's disease patients having a higher proportion of larger and rounder alpha-synuclein aggregates. By combining the number and morphology of the aggregates, a new biomarker with improved accuracy for early Parkinson's disease diagnosis was constructed.
ANALYTICAL CHEMISTRY
(2023)
Review
Neurosciences
Hai-Shan Jiao, Peng Yuan, Jin-Tai Yu
Summary: Mutations in the TMEM106B gene are risk factors for various neurodegenerative diseases. Previous understanding of the underlying mechanism focused on the impairment of lysosome biogenesis caused by TMEM106B loss-of-function. However, mutations in TMEM106B increase its expression level, thus the molecular process linking these mutations to the apparent disruption in TMEM106B function remains mysterious.
MOLECULAR NEURODEGENERATION
(2023)
Article
Biochemistry & Molecular Biology
Harshitha Santhosh Kumar, James Moore, Adrian C. Steiner, Emmanuel Sotirakis, Benjamin Schaerli, Patricia Isnard-Petit, Kader Thiam, David P. Wolfer, Erik C. Boettger
Summary: This study investigates the role of protein homeostasis in the accumulation of Alzheimer's associated protein A beta and levels of associated Tau phosphorylation. Surprisingly, disruptions in protein homeostasis did not significantly affect A beta accumulation and phosphorylated Tau levels.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Medicine, General & Internal
Thamonwan Diteepeng, Federica del Monte, Marco Luciani
Summary: This review discusses the recent progress in understanding protein misfolding and compromised protein quality control in cardiovascular diseases, highlighting the lack of successful translation from preclinical models to clinical settings. More collaboration between basic scientists and clinicians is needed to develop specific biomarkers and therapeutic strategies to target proteotoxicity in CVD patients.
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Chemistry, Multidisciplinary
Dalia Naser, Michael Tarasca, Bruna Siebeneichler, Anna Schaefer, Harmeen K. Deol, Tyler G. B. Soule, Johnathan Almey, Susan Kelso, Gyana G. Mishra, Hilary Simon, Elizabeth M. Meiering
Summary: Protein aggregation plays a central role in aging, disease and biotechnology. This study used NMR quenched amide hydrogen/deuterium exchange, FTIR, and Congo red binding to analyze cellular inclusion bodies of immature human superoxide dismutase mutants. The results revealed multiple aggregation-prone regions in SOD1 and provided insights into the pathways of aggregation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Applied
Yuan Peng, Chuanyang Wang, Jian Yu, Jinhong Wu, Faxiang Wang, Yongle Liu, Xianghong Li
Summary: This study investigated the intermolecular interactions and self-assembly mechanism of rice glutelin amyloid fibril aggregates using experimental and computer simulation methods. The addition of NaCl and SDS promoted the aggregation of the fibrils, while the addition of urea caused degradation and depolymerization. Hydrogen bonding primarily drove the formation of the common cross 8-sheet structure, with hydrophobic and electrostatic interactions also involved. Molecular dynamics simulations confirmed the nucleation-elongation mechanism for the formation of the aggregates. Understanding the self-assembly pattern of amyloid fibril aggregates derived from food protein is crucial for their design and practical application.
FOOD HYDROCOLLOIDS
(2023)
Review
Food Science & Technology
Trui Luyckx, Charlotte Grootaert, Margarita Monge-Morera, Jan A. Delcour, Frederic Rousseau, Joost Schymkowitz, John Van Camp
Summary: This review provides a comprehensive overview of the biological fate and potential health implications of ingested amyloid-like protein fibrils (ALFs) in both healthy and predisposed individuals. The study concludes that the health impact of ALF consumption remains widely understudied and merits additional research efforts to determine the exact extent to which ALF ingestion may influence the general health status.
MOLECULAR NUTRITION & FOOD RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Juan R. Peinado, Kriti Chaplot, Timothy S. Jarvela, Edward M. Barbieri, James Shorter, Iris Lindberg
Summary: As neurons age, protein homeostasis becomes less efficient, leading to misfolding and aggregation of proteins. Chaperone proteins play a vital role in maintaining cellular protein homeostasis and chaperone-based therapies may be useful in preventing the development of neurodegenerative diseases. In this study, the researchers found that proSAAS, a small secreted neuronal protein, can interact with protein aggregates in the cytoplasm and form liquid droplet-like spheres. These proSAAS spheres can encapsulate TDP-43 aggregates, and the interaction is driven by specific sequences in the proSAAS protein.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Giulia Vecchi, Pietro Sormanni, Benedetta Mannini, Andrea Vandelli, Gian Gaetano Tartaglia, Christopher M. Dobson, F. Ulrich Hartl, Michele Vendruscolo
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Biochemistry & Molecular Biology
Ryan Limbocker, Benedetta Mannini, Rodrigo Cataldi, Shianne Chhangur, Aidan K. Wright, Ryan P. Kreiser, J. Alex Albright, Sean Chia, Johnny Habchi, Pietro Sormanni, Janet R. Kumita, Francesco S. Ruggeri, Christopher M. Dobson, Fabrizio Chiti, Francesco A. Aprile, Michele Vendruscolo
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Multidisciplinary Sciences
Francesco A. Aprile, Pietro Sormanni, Marina Podpolny, Shianne Chhangur, Lisa-Maria Needham, Francesco S. Ruggeri, Michele Perni, Ryan Limbocker, Gabriella T. Heller, Tomas Sneideris, Tom Scheidt, Benedetta Mannini, Johnny Habchi, Steven F. Lee, Patricia C. Salinas, Tuomas P. J. Knowles, Christopher M. Dobson, Michele Vendruscolo
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Review
Biochemistry & Molecular Biology
Ryan P. Kreiser, Aidan K. Wright, Natalie R. Block, Jared E. Hollows, Lam T. Nguyen, Kathleen LeForte, Benedetta Mannini, Michele Vendruscolo, Ryan Limbocker
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Correction
Biology
Rodrigo Cataldi, Sean Chia, Katarina Pisani, Francesco S. Ruggeri, Catherine K. Xu, Tomas Sneideris, Michele Perni, Sunehera Sarwat, Priyanka Joshi, Janet R. Kumita, Sara Linse, Johnny Habchi, Tuomas P. J. Knowles, Benedetta Mannini, Christopher M. Dobson, Michele Vendruscolo
Summary: A correction to the paper has been published.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biology
Rodrigo Cataldi, Sean Chia, Katarina Pisani, Francesco S. Ruggeri, Catherine K. Xu, Tomas Sneideris, Michele Perni, Sunehera Sarwat, Priyanka Joshi, Janet R. Kumita, Sara Linse, Johnny Habchi, Tuomas P. J. Knowles, Benedetta Mannini, Christopher M. Dobson, Michele Vendruscolo
Summary: Cataldi et al. investigates the impact of the dopamine derivative DOPAL on the formation of A beta peptide oligomers. They found that DOPAL promotes the formation of stable A beta oligomers that increase cytosolic calcium levels and generate reactive oxygen species, causing toxicity to neuroblastoma cells. This study reveals a connection between A beta aggregation and crucial biochemical processes regulating cellular homeostasis in the brain.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Giulia Fani, Benedetta Mannini, Giulia Vecchi, Roberta Cascella, Cristina Cecchi, Christopher M. Dobson, Michele Vendruscolo, Fabrizio Chiti
Summary: Alzheimer's disease, the most common form of dementia, is characterized by the toxicity mechanism of Aβ oligomers through perturbing the mechanical properties of lipid membranes sensed by NMDA and AMPA receptors.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Immunology
Magdalena Leal-Lasarte, Cintia Roodveldt, David Pozo, Fabrizio Chiti, Benedetta Mannini, Christopher M. Dobson, Michele Vendruscolo
Summary: Recent studies show that different types of protein misfolded oligomers have varying effects on the peripheral immune system, with some resembling responses seen in Parkinson's disease and others in Alzheimer's disease. Further research into the impact of protein misfolded oligomers on the immune system could lead to the development of blood-based diagnostic methods.
Article
Multidisciplinary Sciences
Michele Perni, Benedetta Mannini, Catherine K. Xu, Janet R. Kumita, Christopher M. Dobson, Fabrizio Chiti, Michele Vendruscolo
Summary: Misfolded protein oligomers can diffuse from the intestinal lumen to other tissues in C. elegans, leading to disease phenotypes and toxic effects. Pre-incubation with a molecular chaperone or a protein aggregation inhibitor reduces oligomer absorption and mitigates toxic effects in the worms.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Ryan Limbocker, Roxine Staats, Sean Chia, Francesco S. Ruggeri, Benedetta Mannini, Catherine K. Xu, Michele Perni, Roberta Cascella, Alessandra Bigi, Liam R. Sasser, Natalie R. Block, Aidan K. Wright, Ryan P. Kreiser, Edward T. Custy, Georg Meisl, Silvia Errico, Johnny Habchi, Patrick Flagmeier, Tadas Kartanas, Jared E. Hollows, Lam T. Nguyen, Kathleen LeForte, Denise Barbut, Janet R. Kumita, Cristina Cecchi, Michael Zasloff, Tuomas P. J. Knowles, Christopher M. Dobson, Fabrizio Chiti, Michele Vendruscolo
Summary: The study reveals the mechanism by which aminosterols modulate the aggregation of Aβ and α-S and suppress their toxicity, indicating that these compounds can inhibit toxicity by displacing toxic oligomeric species from cellular membranes.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Biology
Priyanka Joshi, Michele Perni, Ryan Limbocker, Benedetta Mannini, Sam Casford, Sean Chia, Johnny Habchi, Johnathan Labbadia, Christopher M. Dobson, Michele Vendruscolo
Summary: Joshi et al. identified two human metabolites, carnosine and kynurenic acid, that rescue a C. elegans model of Alzheimer's disease by inhibiting the aggregation of amyloid beta peptide in vivo. These metabolites trigger a cytosolic unfolded protein response through the transcription factor HSF-1 and molecular chaperones DNJ-12 and DNJ-19, providing mechanistic links between metabolite homeostasis and protein homeostasis for interventions against neurodegenerative diseases.
COMMUNICATIONS BIOLOGY
(2021)
Correction
Biology
Priyanka Joshi, Michele Perni, Ryan Limbocker, Benedetta Mannini, Sam Casford, Sean Chia, Johnny Habchi, Johnathan Labbadia, Christopher M. Dobson, Michele Vendruscolo
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Catherine K. Xu, Marta Castellana-Cruz, Serene W. Chen, Zhen Du, Georg Meisl, Aviad Levin, Benedetta Mannini, Laura S. Itzhaki, Tuomas P. J. Knowles, Christopher M. Dobson, Nunilo Cremades, Janet R. Kumita
Summary: A wide range of oligomeric structures are formed during the aggregation of proteins associated with neurodegenerative diseases. The soluble oligomers are considered to be toxic in the related disorders. This study identified a novel structural polymorphism within G51D oligomers and found that the helical structural content correlates with the level of cellular dysfunction.
Article
Biochemistry & Molecular Biology
Diana C. Rodriguez Camargo, Sean Chia, Joseph Menzies, Benedetta Mannini, Georg Meisl, Martin Lundqvist, Christin Pohl, Katja Bernfur, Veronica Lattanzi, Johnny Habchi, Samuel Ia Cohen, Tuomas P. J. Knowles, Michele Vendruscolo, Sara Linse
Summary: The aggregation of human islet amyloid polypeptide (IAPP) is associated with type II diabetes, with IAPP oligomers identified as the most cytotoxic species. Secondary nucleation is the main mechanism for generating new aggregates, with toxicity peaking at the maximum secondary nucleation rate. Compounds targeting IAPP secondary nucleation may be the most effective therapeutic candidates for type II diabetes.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Multidisciplinary Sciences
Gabriella T. Heller, Francesco A. Aprile, Thomas C. T. Michaels, Ryan Limbocker, Michele Perni, Francesco Simone Ruggeri, Benedetta Mannini, Thomas Lohr, Massimiliano Bonomi, Carlo Camilloni, Alfonso De Simone, Isabella C. Felli, Roberta Pierattelli, Tuomas P. J. Knowles, Christopher M. Dobson, Michele Vendruscolo