Article
Biochemistry & Molecular Biology
Aruna K. Mora, Sushant Murudkar, Neelam Shivran, Soumyaditya Mula, Subrata Chattopadhyay, Sukhendu Nath
Summary: Protein oligomers, formed under physiological stress, are neurotoxic and linked to neurological diseases. Early detection is crucial, and a new NIR-emitting fluorescent probe has been developed for this purpose. The probe not only detects matured fibrils but also probes oligomer formation, showing potential for in vivo imaging.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Addison Frese, Cody Goode, Kiryl Zhaliazka, Aidan P. Holman, Tianyi Dou, Dmitry Kurouski
Summary: The aggregation of misfolded proteins is the fundamental molecular cause of severe pathologies such as Alzheimer's and Parkinson's diseases. Lipids are found to play a vital role in this process. In this study, the researchers investigated the impact of the length and saturation of fatty acids in phosphatidylserine (PS) on lysozyme aggregation. The results showed that both factors influenced the aggregation rate of insulin. The presence of double bonds in fatty acids accelerated the rate of insulin aggregation relative to PS with fully saturated fatty acids.
Review
Biochemistry & Molecular Biology
Parveen Salahuddin, Munazza Tamkeen Fatima, Vladimir N. Uversky, Rizwan Hasan Khan, Zeyaul Islam, Mohammad Furkan
Summary: Neurodegenerative diseases are characterized by the abnormal loss of neurons, with common pathogenic mechanisms involving misfolding and aggregation of proteins. Accumulating evidence suggests that amyloid oligomers, not fibrils, are the most toxic species causing AD and PD.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Qize Xuan, Jiaxin He, Wenxue Zhang, Wei Zhang, Qi Zhang, Yao Zhou, Anqi Wei, Hao Wang, Hui Li, Chao Chen, Ping Wang
Summary: This study successfully prepared three different morphological and structural phenol-soluble modulin alpha 3 (PSM alpha 3) assemblies using the strategy of salt-inducing assembly polymorphism. It was found that amyloid fibrillation was essential for enhancing the cytotoxicity of PSM alpha 3, and the size and structure of PSM alpha 3 fibrils played a crucial role in cytotoxicity. The cytotoxicity was achieved through a membrane-disrupting mechanism, with different fibril types causing membrane thinning or perforation.
Article
Biochemistry & Molecular Biology
Lei Gu, Zhefeng Guo
Summary: Formation of amyloid oligomers and fibrils, underlying neurodegenerative diseases like Alzheimer's, involves interactions with cellular membranes. The conversion of Aβ42 globulomers to fibrils in the presence of DOPC liposomes suggests a dynamic nature of interactions between Aβ oligomers and membranes. Lipid membranes can reduce membrane-disrupting activities caused by Aβ oligomers by converting them to fibrils.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Carly K. Schissel, Somesh Mohapatra, Justin M. Wolfe, Colin M. Fadzen, Kamela Bellovoda, Chia-Ling Wu, Jenna A. Wood, Annika B. Malmberg, Andrei Loas, Rafael Gomez-Bombarelli, Bradley L. Pentelute
Summary: The study demonstrates that deep learning can decipher design principles to generate highly active biomolecules, such as Mach proteins, which are capable of delivering antisense cargo efficiently without toxicity in mice. This approach combines high-throughput experimentation with a deep-learning method inspired by directed evolution, representing molecular structures as topological fingerprints.
Article
Chemistry, Physical
Adolfo B. Poma, Tran Thi Minh Thu, Lam Tang Minh Tri, Hoang Linh Nguyen, Mai Suan Li
Summary: Alzheimer's disease is a neurodegenerative disorder associated with A beta peptide aggregation. Recent experiments suggest that oligomers are more toxic than mature fibrils, leading researchers to investigate factors that may influence the properties of oligomers.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Review
Biochemistry & Molecular Biology
Ajit Kumar Bishoyi, Pratiksha H. Roham, Kavitha Rachineni, Shreyada Save, M. Asrafuddoza Hazari, Shilpy Sharma, Ashutosh Kumar
Summary: The overexpression of hIAPP in T2DM is associated with misfolding of the peptide, formation of amyloid deposits, and death and dysfunction of pancreatic beta-islets. Studies have shown that during aggregation, hIAPP undergoes conformational changes from helix to beta-sheet and finally to left-handed helical aggregates, with intermediates causing cellular toxicity.
BIOLOGICAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Jiangtao Zhou, Ting Li, Mohammad Peydayesh, Mattia Usuelli, Viviane Lutz-Bueno, Jie Teng, Li Wang, Raffaele Mezzenga
Summary: Amyloid functional materials derived from oat globulin show diverse functionalities with rich polymorphism, reversible and irreversible fibrillization processes. These materials can be applied in water purification, sensors, and electrodes, with demonstrated sustainability against other protein sources for environmentally-efficient advanced materials and technologies.
Review
Biochemistry & Molecular Biology
Roberta Cascella, Cristina Cecchi
Summary: Alzheimer's disease is a common age-related neurodegenerative disorder characterized by amyloid beta-protein deposition and neurofibrillary tangles, leading to cognitive decline and dementia. Despite extensive research, the exact mechanisms underlying AD remain unknown and effective treatment is not available.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
D. Santorelli, S. Rocchio, F. Fata, I Silvestri, F. Angelucci, F. Imperi, D. Marasco, C. Diaferia, L. Gigli, N. Demitri, L. Federici, A. Di Matteo, C. Travaglini-Allocatelli
Summary: The study found that ribosome-binding factor A folds via a 3-state mechanism in vitro and can form fibrils with a cross-beta structure. Additionally, the research suggests that the folding intermediate of PaRbfA may expose amyloidogenic regions, potentially acting as aggregation nuclei in fibril formation.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
Article
Chemistry, Physical
Debasis Saha, Biman Jana
Summary: This study investigates the intermediates in the fibril formation pathway of A beta(13-42) oligomers and identifies their stable conformations and structural features. Residues 30-36 are found to play a crucial role in fibril formation.
Article
Biochemistry & Molecular Biology
Daniele Santorelli, Francesca Troilo, Francesca Fata, Francesco Angelucci, Nicola Demitri, Giorgio Giardina, Luca Federici, Flavia Catalano, Adele Di Matteo, Carlo Travaglini-Allocatelli
Summary: K-homology (KH) domains are structurally conserved domains found in proteins of different origins, which play important roles in various functions. Mutations in KH domains have been associated with multiple diseases, including fragile X syndrome. By characterizing the folding mechanism of a specific KH domain, it was found that transient intermediate accumulates and the domain has the propensity to form amyloid-like aggregates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Xiuhua Yin, Hong Zhou, Mengling Zhang, Juan Su, Xiao Wang, Sijie Li, Zaixing Yang, Zhenhui Kang, Ruhong Zhou
Summary: This study discovered an ultra-small nanodot, C3N, that inhibits the aggregation of A beta peptides and improves behavioral deficits in an AD mouse model. C3N nanodots not only reduce the levels of A beta peptides but also protect neurons and synapses.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Kiryl Zhaliazka, Mikhail Matveyenka, Dmitry Kurouski
Summary: Abrupt aggregation of amyloid beta(1-42) (Aβ) peptide is a hallmark of Alzheimer's disease (AD), and lipids have been found to uniquely alter the rate and structure of Aβ(1-42) aggregation. In this study, the effect of phosphatidylcholine (PC), cardiolipin (CL), and cholesterol (Chol) on Aβ(1-42) aggregation was investigated. The results showed that these lipids significantly accelerated the rate of fibril formation and modified the secondary structure of Aβ(1-42) aggregates.