Article
Biochemistry & Molecular Biology
Yang Gao, Stefan Wennmalm, Bengt Winblad, Sophia Schedin-Weiss, Lars O. Tjernberg
Summary: Through FRET imaging, Aβ42 oligomerization was successfully detected in primary neurons, showing that Aβ42 oligomerized in lysosomes/late endosomes in a concentration-dependent manner. These findings contribute to a better understanding of Aβ42 oligomerization in neurons.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Rodrigo Perez-Arancibia, Jose Luis Ordonez, Alexis Rivas, Philippe Pihan, Alfredo Sagredo, Ulises Ahumada, Andres Barriga, Ivette Seguel, Cesar Cardenas, Rene L. Vidal, Claudio Hetz, Carla Delporte
Summary: The study revealed that extracts from Chilean-native Ugni molinae berries contain anti-inflammatory and antioxidant components, with inhibitory effects on protein aggregation in Alzheimer's and Huntington's disease models. Particularly, extracts from the 19-1 genotype showed significant reduction in polyglutamine peptide aggregation. Additionally, the presence of flavonoids, phenolic acids, and ellagitannins in the extracts was found to be correlated with their protective effects on protein aggregation.
Review
Biochemistry & Molecular Biology
Anna Sulatskaya, Anastasiia O. Kosolapova, Alexander G. Bobylev, Mikhail Belousov, Kirill S. Antonets, Maksim Sulatsky, Irina M. Kuznetsova, Konstantin K. Turoverov, Olesya Stepanenko, Anton A. Nizhnikov
Summary: Both amyloids and beta-barrel proteins have beta-sheet-rich structures, with the latter being able to form functional amyloids in vivo. These beta-barrel amyloid proteins can interact with each other and form toxic oligomers, potentially contributing to the development of amyloidoses. Rapidly growing discoveries suggest that the number and diversity of functions of amyloid-forming beta-barrel proteins are significantly greater than currently understood.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Nan Yuan, Lianmeng Ye, Yan Sun, Hao Wu, Zhengpan Xiao, Wanmeng Fu, Zuqian Chen, Yechun Pei, Yi Min, Dayong Wang
Summary: The major pathological feature of Alzheimer's disease (AD) is the aggregation of amyloid beta peptide (A beta) in the brain. Inhibition of A beta(42) aggregation may prevent the advancement of AD. This study found that arginine dipeptide (RR) was the most effective at interfering with A beta(42) polymerization and reducing its toxicity, including cell death, reactive oxygen species (ROS) production, and apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Martina Bortolami, Fabiana Pandolfi, Valeria Tudino, Antonella Messore, Valentina Noemi Madia, Daniela De Vita, Roberto Di Santo, Roberta Costi, Isabella Romeo, Stefano Alcaro, Marisa Colone, Annarita Stringaro, Alba Espargaro, Raimon Sabate, Luigi Scipione
Summary: Alzheimer's disease is a neurodegenerative disorder associated with age and is a major medical challenge. The current standard treatment involves the use of cholinesterase inhibitors, but their effectiveness is limited. Therefore, researchers have developed new catalysts with antioxidant properties and metal chelating abilities. Recent studies have found that some compounds have higher selectivity against BChE and show potential in preventing disease progression, with low toxicity on brain cells.
Article
Biochemistry & Molecular Biology
Martina Bortolami, Fabiana Pandolfi, Valeria Tudino, Antonella Messore, Valentina Noemi Madia, Daniela De Vita, Roberto Di Santo, Roberta Costi, Isabella Romeo, Stefano Alcaro, Marisa Colone, Annarita Stringaro, Alba Espargaro, Raimon Sabate, Luigi Scipione
Summary: A new series of dual binding site inhibitors were designed to effectively inhibit cholinesterases while possessing antioxidant and anti-aggregation properties against dementia-related proteins. These compounds exhibit low cytotoxicity and are predicted to be able to penetrate the blood-brain barrier.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Chemistry, Medicinal
Prajakta H. Patil, Sumit Birangal, G. Gautham Shenoy, Mahadev Rao, Sandeep Kadari, Amit Wankhede, Himanshu Rastogi, Tarun Sharma, Jakir Pinjari, Jagadish Puralae Channabasavaiah
Summary: Curcumin and quercetin can inhibit the metabolism of CDK inhibitors, potentially causing herb-drug interactions and should be cautiously used to avoid therapeutic failure.
PHYTOTHERAPY RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Alexandre Chappard, Craig Leighton, Rebecca S. S. Saleeb, Kiani Jeacock, Sarah R. R. Ball, Katie Morris, Owen Kantelberg, Ji-Eun Lee, Elsa Zacco, Annalisa Pastore, Margaret Sunde, David J. J. Clarke, Patrick Downey, Tilo Kunath, Mathew H. H. Horrocks
Summary: Protein misfolding and aggregation are common features of neurogenerative disorders. Single-molecule techniques have allowed the characterization of these protein aggregates, previously inaccessible with traditional methods. In this study, we employed a high affinity antibody labeled with orthogonal fluorophores, along with fast-flow microfluidics and single-molecule confocal microscopy, to specifically detect alpha-synuclein in biologically relevant samples.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Yanxian Zhang, Yijing Tang, Yonglan Liu, Dong Zhang, Jie Zheng
Summary: This research proposes a strategy for designing new, multi-target amyloid aggregation-prone fragments and their antimicrobial agent conjugates, achieving improved multifunctionality of amyloid inhibition, antimicrobial activity, and amyloid imaging. By selecting two APFs and constructing hybrid peptides, the study successfully inhibits amyloid aggregation, reduces cell toxicity, prevents microbial growth, and introduces fluorescence imaging for PMDs. This work not only explores new potential antimicrobial and anti-amyloid drugs for PMDs, but also enhances understanding of the pathological links between protein aggregation and microbial infection along the gut-brain axis.
ADVANCED FUNCTIONAL MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Yu Zhang, Yuying Liu, Wenhui Zhao, Yunxiang Sun
Summary: The study demonstrates that SWCNT-OH has excellent anti-amyloid properties, inhibiting the fibrillization of beta 2m(21)(-)(31) peptides and destroying pre-formed proto-fibrils.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemical Research Methods
Mantas Ziaunys, Kamile Mikalauskaite, Andrius Sakalauskas, Vytautas Smirnovas
Summary: The aggregation of amyloidogenic proteins is related to various diseases, with limited treatment options currently available. The challenge in the discovery of potential anti-amyloid molecules lies in identifying the actual inhibitors from complex mixtures. This study successfully scavenged potential aggregation-inhibiting molecules from different compounds and effectively separated them from the aggregates.
BIOTECHNOLOGY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Hanna Nieznanska, Solomiia Boyko, Robert Dec, Maria Jolanta Redowicz, Wojciech Dzwolak, Krzysztof Nieznanski
Summary: The PKA-phosphorylated K18.280 oligomers are shown to be toxic to hippocampal neurons, leading to cell death, while the soluble N-terminal fragment N1 of prion protein (PrP) can protect neurons from the cytotoxic effects induced by these oligomers. These findings support the hypothesis on the neurotoxicity of Tau oligomers and the neuroprotective role of PrP-derived fragments in AD and other tauopathies, which could be valuable for the development of therapeutic strategies for these diseases.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Chemistry, Physical
Hongru Ding, Pavana Siddhartha Kollipara, Linhan Lin, Yuebing Zheng
Summary: Optothermal tweezers, with superior manipulation capability at low optical intensity, are limited by implicit understanding of the working mechanism. By revealing the atomistic view of opto-thermo-electro-mechanic coupling, we have developed high-performance tweezers using low-concentrated electrolytes and demonstrated their efficiency in separating colloidal particles based on surface charge differences.
Article
Biochemistry & Molecular Biology
Peter K. Windsor, Stephen P. Plassmeyer, Dominic S. Mattock, Jonathan C. Bradfield, Erika Y. Choi, Bill R. Miller, Byung Hee Han
Summary: The study found that a class of biflavonoids can promote the disaggregation of Aβ fibrils, with varying potency due to structural differences. Computational analysis provided the first atomistic details for the mechanism of Aβ disaggregation by biflavonoids. Molecular docking analysis showed that biflavonoids preferably bind to the aromatic-rich, partially ordered N-termini of Aβ fibrils via pi-pi interactions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Environmental Sciences
Samal Kaumbekova, Mehdi Amouei Torkmahalleh, Dhawal Shah
Summary: Long-term exposure to ambient ultrafine particles increases the risk of neurodegenerative diseases like Alzheimer's disease. This study used molecular dynamics simulations to investigate the effect of polycyclic aromatic hydrocarbons (PAHs) on the formation of A beta(42) oligomers. It was found that a specific PAH, Benzo[a]Pyrene (B[a]P), accelerated the formation of oligomers, while other concentrations of B[a]P suppressed the oligomerization process.
Article
Clinical Neurology
Jing Di, Ibrar Siddique, Zizheng Li, Ghattas Malki, Simon Hornung, Suman Dutta, Ian Hurst, Ella Ishaaya, Austin Wang, Sally Tu, Ani Boghos, Ida Ericsson, Frank-Gerrit Klaerner, Thomas Schrader, Gal Bitan
Summary: The study demonstrated that CLR01 directly targets tau protein to ameliorate Alzheimer's disease pathology. However, limitations of the study, such as a relatively short treatment period and high variability in the model, lowered the statistical significance of some outcomes.
ALZHEIMERS RESEARCH & THERAPY
(2021)
Article
Clinical Neurology
Suman Dutta, Simon Hornung, Adira Kruayatidee, Katherine N. Maina, Irish del Rosario, Kimberly C. Paul, Darice Y. Wong, Aline Duarte Folle, Daniela Markovic, Jose-Alberto Palma, Geidy E. Serrano, Charles H. Adler, Susan L. Perlman, Wayne W. Poon, Un Jung Kang, Roy N. Alcalay, Miriam Sklerov, Karen H. Gylys, Horacio Kaufmann, Brent L. Fogel, Jeff M. Bronstein, Beate Ritz, Gal Bitan
Summary: The study found that measuring α-syn in exosomes from blood can effectively distinguish between patients with PD and MSA with high sensitivity and specificity. A multinomial logistic model combining α-syn concentration, exosome concentration, and a ratio between α-syn concentrations in specific exosomes showed promising results in separating PD from MSA.
ACTA NEUROPATHOLOGICA
(2021)
Correction
Clinical Neurology
Suman Dutta, Simon Hornung, Adira Kruayatidee, Katherine N. Maina, Irish del Rosario, Kimberly C. Paul, Darice Y. Wong, Aline Duarte Folle, Daniela Markovic, Jose-Alberto Palma, Geidy E. Serrano, Charles H. Adler, Susan L. Perlman, Wayne W. Poon, Un Jung Kang, Roy N. Alcalay, Miriam Sklerov, Karen H. Gylys, Horacio Kaufmann, Brent L. Fogel, Jeff M. Bronstein, Beate Ritz, Gal Bitan
Summary: A correction to the paper has been published.
ACTA NEUROPATHOLOGICA
(2021)
Review
Biochemistry & Molecular Biology
Kazuma Murakami, Naotaka Izuo, Gal Bitan
Summary: Aptamers, similar to antibodies, are oligonucleotides selected based on their affinity for bioactive molecules. They have advantages such as small size, easy synthesis, high stability, and low immunogenicity. However, developing aptamers against amyloidogenic proteins, which are relevant to neurodegenerative diseases, is challenging due to their conformational instability and heterogeneity. Recent advancements in chemical tethering of aptagens, high-throughput sequencing-based analysis, and internalization technologies have helped overcome some of these challenges. This review highlights the preclinical application of antiamyloid aptamers to central nervous system therapy.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Clinical Neurology
Jose-Alberto Palma, Jose Martinez, Patricio Millar Vernetti, Thong Ma, Miguel A. Perez, Judy Zhong, Yingzhi Qian, Suman Dutta, Katherine N. Maina, Ibrar Siddique, Gal Bitan, Benjamin Ades-Aron, Timothy M. Shepherd, Un J. Kang, Horacio Kaufmann
Summary: The efficacy and safety of sirolimus in patients with multiple system atrophy (MSA) were investigated in this study. The results showed that sirolimus treatment for 48 weeks was futile in slowing the progression of MSA and had no effect on biomarkers compared to placebo. Changes in blood neurofilament light chain (NfL) and whole brain atrophy were identified as promising biomarkers of disease progression for future clinical trials.
MOVEMENT DISORDERS
(2022)
Article
Biochemistry & Molecular Biology
Hedieh Shahpasand-Kroner, Jennifer Portillo, Carter Lantz, Paul M. Seidler, Natalie Sarafian, Joseph A. Loo, Gal Bitan
Summary: This study analyzed the initial oligomerization of six tau isoforms in the absence of posttranslational modifications or other manipulations. The results showed that three-repeat (3R) isoforms are more prone to form oligomers than four-repeat (4R) isoforms. Known tau aggregation inhibitors had little or no effect on the initial oligomerization.
Correction
Biochemistry & Molecular Biology
Sharmistha Sinha, Zhenming Du, Panchanan Maiti, Frank-Gerrit Klarner, Thomas Schrader, Chunyu Wang, Gal Bitan
ACS CHEMICAL NEUROSCIENCE
(2022)
Editorial Material
Neurosciences
Hash Brown Taha, Brian Kearney, Gal Bitan
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Suman Dutta, Simon Hornung, Hash Brown Taha, Karl Biggs, Ibrar Siddique, Lea M. Chamoun, Hedieh Shahpasand-Kroner, Carter Lantz, Marcos Herrera-Vaquero, Nadia Stefanova, Joseph A. Loo, Gal Bitan
Summary: A new method for sensitive detection of pS129-alpha-syn has been developed, which can be applied to various biological samples. This method provides a valuable tool for discovering and monitoring neurodegenerative diseases associated with abnormal accumulation of synaptic proteins.
ACS CHEMICAL NEUROSCIENCE
(2023)
Review
Clinical Neurology
Suman Dutta, Simon Hornung, Hash Brown Taha, Gal Bitan
Summary: Extracellular vesicles (EVs) are small particles enclosed by a lipid bilayer, which play a role in intercellular communication by transporting various biomaterials. In neurodegenerative diseases, EVs may carry toxic proteins and facilitate their spread in the central nervous system. These EVs can be found in body fluids like saliva, tears, and urine, making them a potential source of biomarkers. Despite the progress in utilizing CNS-originating EVs for biomarker studies, certain technical challenges, such as isolating cell type-specific EVs and validating their origin, still need to be addressed.
ACTA NEUROPATHOLOGICA
(2023)
Editorial Material
Geriatrics & Gerontology
Suman Dutta, Miriam Sklerov, Charlotte E. Teunissen, Gal Bitan
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Letter
Neurosciences
Hash Brown Taha, Simon Hornung, Suman Dutta, Leony Fenwick, Otmane Lahgui, Kathryn Howe, Nour Elabed, Irish del Rosario, Darice Y. Y. Wong, Aline Duarte Folle, Daniela Markovic, Jose-Alberto Palma, Un Jung Kang, Roy N. N. Alcalay, Miriam Sklerov, Horacio Kaufmann, Brent L. L. Fogel, Jeff M. M. Bronstein, Beate Ritz, Gal Bitan
TRANSLATIONAL NEURODEGENERATION
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Daniela Vilasboas-Campos, Sara Duarte-Silva, Daniela Monteiro-Fernandes, Joana Pereira-Sousa, Andreia Neves-Carvalho, Gal Bitan, Sandra Macedo-Ribeiro, Alexandra Silva, Ana Luisa Carvalho, Andreia Teixeira-Castro, Patricia Maciel
JOURNAL OF NEUROCHEMISTRY
(2022)
Correction
Biochemistry & Molecular Biology
Panchanan Maiti, Roberto Piacentini, Cristian Ripoli, Claudio Grassi, Gal Bitan
BIOCHEMICAL JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Ravit Malishev, Nir Salinas, James Gibson, Angela Bailey Eden, Joel Mieres-Perez, Yasser B. Ruiz-Blanco, Orit Malka, Sofiya Kolusheva, Frank-Gerrit Klaemer, Thomas Schrader, Elsa Sanchez-Garcia, Chunyu Wang, Meytal Landau, Gal Bitan, Raz Jelinek
Summary: This study demonstrates that molecular tweezers can modulate biofilm formation of Staphylococcus aureus, with CLR01 significantly inhibiting biofilm formation and disrupting PSM alpha 1 assembly, while CLR05, containing methylenecarboxylate units, disrupts biofilm more strongly despite lower lysine residues affinity. Molecular tweezers may serve as potent biofilm inhibitors and antibacterial agents against bacteria producing biofilms and PSM.
CELL CHEMICAL BIOLOGY
(2021)