Review
Biochemistry & Molecular Biology
Chuli Song, Tianyu Zhang, Yingjiu Zhang
Summary: Soluble aggregation and deposition of A beta 42 are the initial pathological hallmarks of Alzheimer's disease. Anti-A beta 42 antibodies can inhibit the aggregation and toxicity of A beta 42, but their epitope specificity affects their binding affinity for different A beta 42 species.
Article
Engineering, Biomedical
Bibin Anand, Qi Wu, Maryam Nakhaei-Nejad, Govindarajan Karthivashan, Lyudmyla Dorosh, Sara Amidian, Abhishek Dahal, Xiuju Li, Maria Stepanova, Holger Wille, Fabrizio Giuliani, Satyabrata Kar
Summary: Native PLGA nanoparticles show therapeutic potential in the treatment of Alzheimer's disease by suppressing aggregation of beta-amyloid peptides, triggering their disassembly, reducing phosphorylation of tau protein, enhancing neuronal viability, and attenuating memory deficits and A beta levels in animal models of AD.
BIOACTIVE MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
William J. Howitz, Gretchen Guaglianone, Kate J. McKnelly, Katelyn Haduong, Shareen N. Ashby, Mohamed Laayouni, James S. Nowick
Summary: This study investigates the role of charge in the oligomeric assembly, toxicity, and membrane destabilization of peptides derived from A beta and its familial mutants. The findings suggest that the charge of the amino acid side chain, rather than its size or hydrophobicity, accounts for the differences in the behavior of the E22 familial mutants of A beta.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Xueling Yuan, Zhuo Wang, Lei Zhang, Rubo Sui, Suliman Khan
Summary: Liquiritigenin was found to be an efficient inhibitor of tau amyloid fibril formation, reducing ROS and caspase-3 activity, and increasing CAT activity to alleviate neurotoxicity.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Neurosciences
Zi-Xuan Tan, Fang Dong, Lin-Yu Wu, Ya-Shuo Feng, Feng Zhang
Summary: Alzheimer's disease is a major burden on global healthcare systems, and effective treatments are needed. Accumulation of neurotoxic beta-amyloid peptide (A beta) is a feature of AD, but medications targeting its reduction have yet to prove effective. Physical exercise has benefits for AD, including reducing A beta deposition to alleviate symptoms.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Kazuma Murakami, Shiori Horii, Mizuho Hanaki, Kazuhiro Irie
Summary: The aggregation of Amyloid beta 42 in Alzheimer's disease involves nucleation and elongation phases. An orcein derivative, O4, has been shown to convert toxic oligomers into inert fibrils. Screening natural products for compounds that delay nucleation and promote elongation revealed several candidates that reduce the toxicity of Amyloid beta 42 against neuroblastoma cells. These compounds may interact with Amyloid beta 42 to shift its equilibrium from toxic oligomers to inert fibrils.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Microbiology
George Tetz, Victor Tetz
Summary: The study found that bacterial extracellular DNA can trigger Aβ protein aggregation, with the acceleration depending on the DNA concentration and bacterial strain. It suggests that bacterial DNA may play an important role in the pathogenesis of Alzheimer's disease.
Article
Biochemistry & Molecular Biology
Katerina Konstantoulea, Patricia Guerreiro, Meine Ramakers, Nikolaos Louros, Liam D. Aubrey, Bert Houben, Emiel Michiels, Matthias De Vleeschouwer, Yulia Lampi, Luis F. Ribeiro, Joris Wit, Wei-Feng Xue, Joost Schymkowitz, Frederic Rousseau
Summary: The study found that proteins enriched in homologous sequences to Aβ aggregation-prone regions are present in Aβ plaques from AD patients, suggesting heterotypic amyloid interactions may occur. These proteins can modify Aβ assembly kinetics, fibril morphology, and deposition pattern in vitro. Additionally, it was discovered that transient expression of three of these proteins in an Aβ reporter cell line promotes Aβ amyloid aggregation, indicating a potential role of heterotypic APR interactions in amyloid-deposition diseases.
Article
Neurosciences
Meilin Wu, Clifford Z. Liu, Erika A. Barrall, Robert A. Rissman, William J. Joiner
Summary: The study demonstrates the role of Ly6h and NACHO in maintaining the balance of alpha 7 nicotinic acetylcholine receptors, which is disrupted in Alzheimer's disease leading to neurotoxic signaling.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Medicine, Research & Experimental
Sagheer Ahmed, Sidrah Tariq Khan, Muhammad Kazim Zargaham, Arif Ullah Khan, Saeed Khan, Abrar Hussain, Jalal Uddin, Ajmal Khan, Ahmed Al-Harrasi
Summary: Alzheimer's disease is the most common type of dementia affecting the later years of life and will be a major burden on the healthcare system. Despite scientific advancements, there are still no therapies available to stop or slow the progression of the disease. FDA has approved certain drugs for AD treatment, but research also suggests potential benefits from herbal compounds.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Atsushi Michael Kimura, Mayumi Tsuji, Taro Yasumoto, Yukiko Mori, Tatsunori Oguchi, Yuya Tsuji, Masakazu Umino, Asami Umino, Toru Nishikawa, Shiro Nakamura, Tomio Inoue, Yuji Kiuchi, Masahito Yamada, David B. Teplow, Kenjiro Ono
Summary: Accumulation of amyloid beta-protein is a primary mechanism leading to neuronal death in Alzheimer's disease, with protofibrils being a key target for disease-modifying therapy. Previous studies have shown that phenolic compounds like myricetin can inhibit aggregations of beta-amyloid and alpha-synuclein, providing protective effects against AD and Parkinson's disease. This study demonstrates that myricetin can protect against HMW-A beta o-induced neurotoxicity through multiple antioxidant functions, suggesting its potential as a disease-modifying agent for AD.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Chemistry, Medicinal
Misato Tajiri, Ryo Yamada, Mayumi Hotsumi, Koki Makabe, Hiroyuki Konno
Summary: This study describes the total synthesis of berberine and selected analogues, and evaluates their effectiveness as amyloid beta (Aβ) aggregation inhibitors. The key step in the synthesis is the assembly of the berberine framework using an intermolecular Heck reaction. Berberine analog 17, incorporating a tertiary amine moiety, demonstrated good anti-Aβ aggregation activity, water solubility, and minimal toxicity to nerve cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Clinical Neurology
Rina Nakamura, Motomi Konishi, Youichirou Higashi, Motoaki Saito, Toshifumi Akizawa
Summary: In this study, two 5-mer synthetic peptides (GSGNR and GSGFK) were found to inhibit the aggregation of A beta 25-35 and resolve the already aggregated A beta 25-35. The peptide GSGFK was also effective in preventing short-term memory deficits induced by A beta 25-35 in mice and enhancing the phagocytic ability of microglia. These findings suggest that 5-mer peptides could be potential therapeutic drugs for Alzheimer's disease.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Hui Xiao, Lan Duo, James Zhen, Hongsu Wang, Zhefeng Guo
Summary: This study used site-directed spin labeling and EPR spectroscopy to investigate the structure and dynamics of Aβ40 fibrils. The results suggest that the strength of spin exchange interaction in Aβ40 fibrils is primarily determined by static disorder. The entire Aβ40 sequence, except residue D1, is highly ordered, with the hydrophobic regions showing the lowest static disorder. Dynamic disorder is relatively constant across all residues, with residues 22 and 23 having the highest dynamic disorder. Aβ40 fibrils exhibit overall more ordered packing interactions compared to Aβ42 fibrils, and the C-terminal residue is ordered in Aβ40 fibrils but has high static disorder in Aβ42 fibrils. The higher static disorder in Aβ42 fibrils may contribute to increased aggregation through secondary nucleation.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Rohmad Yudi Utomo, Yasunobu Asawa, Satoshi Okada, Hyun Seung Ban, Atsushi Yoshimori, Jorgen Bajorath, Hiroyuki Nakamura
Summary: A new compound B was found to have significantly higher inhibitory activity against Aβ aggregation compared to curcumin, while compound K showed low cytotoxicity on N2A cells and attenuated Aβ-induced cytotoxicity. These findings suggest potential for compound K in preventing neurotoxicity caused by Aβ aggregation.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Joachim M. Matz, Benjamin Drepper, Thorsten B. Blum, Eric van Genderen, Alana Burrell, Peer Martin, Thomas Stach, Lucy M. Collinson, Jan Pieter Abrahams, Kai Matuschewski, Michael J. Blackman
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Microscopy
J. Paul van Schayck, Eric van Genderen, Erik Maddox, Lucas Roussel, Hugo Boulanger, Erik Frojdh, Jan-Pieter Abrahams, Peter J. Peters, Raimond B. G. Ravelli
Article
Biotechnology & Applied Microbiology
Zhenzhen Zhang, Kai Wen, Chao Zhang, Fabrice Laroche, Zhenglong Wang, Qiang Zhou, Zunfeng Liu, Jan Pieter Abrahams, Xiang Zhou
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2020)
Article
Physics, Applied
Pooja Thakkar, Vitaliy A. Guzenko, Peng-Han Lu, Rafal E. Dunin-Borkowski, Jan Pieter Abrahams, Soichiro Tsujino
JOURNAL OF APPLIED PHYSICS
(2020)
Article
Geriatrics & Gerontology
Mari Aksnes, Ann Tiiman, Trine Holt Edwin, Lars Terenius, Nenad Bogdanovic, Vladana Vukojevic, Anne-Brita Knapskog
Summary: Accurate biomarkers for Alzheimer's disease are crucial for early diagnosis and intervention. This study found that levels of nanoplaques in cerebrospinal fluid were increased in patients with AD biomarkers, but did not improve patient classification compared to core biomarkers alone. Dynamic changes in nanoplaque concentration and size throughout AD stages should be further explored.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Biochemical Research Methods
Thorsten B. Blum, Dominique Housset, Max T. B. Clabbers, Eric van Genderen, Maria Bacia-Verloop, Ulrich Zander, Andrew A. McCarthy, Guy Schoehn, Wai Li Ling, Jan Pieter Abrahams
Summary: Electron diffraction in protein crystallography can be improved by limiting dynamical scattering through data collection from thin crystals and using low-noise detectors. Likelihood-based correction can further reduce the dynamical component in refinement, leading to improvements in structural refinement and providing valuable insights into protein function. These advancements enhance the value of macromolecular electron crystallography as a complementary technique in structural biology.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Therese Sorensen, Sarah Leeb, Jens Danielsson, Mikael Oliveberg
Summary: The structural stability of proteins changes significantly upon transfer to the crowded interior of live cells. The intracellular environment behaves like a polyanionic system, which influences protein stability through preferential interactions with globally unfolded proteins. This generic influence of polyanions on protein stability needs to be considered in the evaluation of in vivo data in addition to sequence-specific contributions.
Article
Biochemistry & Molecular Biology
Axel Leppert, Ann Tiiman, Nina Kronqvist, Michael Landreh, Axel Abelein, Vladana Vukojevic, Jan Johansson
Summary: Protein oligomerization is a common strategy to enhance protein function, but difficult to control. A molecular chaperone has been found to inhibit toxic oligomer formation, providing insights into interfering with protein aggregation.
Article
Chemistry, Physical
Naoto Iwakawa, Daichi Morimoto, Erik Walinda, Sarah Leeb, Masahiro Shirakawa, Jens Danielsson, Kenji Sugase
Summary: Research has shown that the aggregation of SOD1 is slowed down in crowded cellular environments, possibly due to the stabilizing effect of the protein crowder lysozyme on an alternative excited invisible state of SOD1, without significantly altering its static structure. This suggests that crowded intracellular environments may inhibit fibril formation of amyloidogenic proteins, shedding light on the role of aggregation in the development of certain diseases.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Biochemistry & Molecular Biology
Xiansha Xiao, Joost Willemse, Patrick Voskamp, Xinmeng Li, Andrea E. Prota, Meindert Lamers, Navraj Pannu, Jan Pieter Abrahams, Gilles P. van Wezel
Summary: The study found that amino acid substitutions in the SsgB protein of Streptomyces bacteria led to ectopically placed septa and diagonally or longitudinally divided cells. This suggests that besides altering FtsZ, aa substitutions in SsgB also play a role in cell division regulation in Streptomyces.
Article
Neurosciences
Mari Aksnes, Hans Christian D. Aass, Ann Tiiman, Trine Holt Edwin, Lars Terenius, Nenad Bogdanovic, Vladana Vukojevic, Anne-Brita Knapskog
Summary: This study aimed to investigate the relationship between fibrillary amyloid aggregates and cytokines in cerebrospinal fluid. The results showed that increased nanoplaque levels were associated with decreased levels of MIP-1 beta, MIP-1 alpha, and IL-8. These associations remained significant even after adjusting for various factors.
TRANSLATIONAL NEURODEGENERATION
(2021)
Article
Neurosciences
Mari Aksnes, Hans Christian D. Aass, Ann Tiiman, Lars Terenius, Nenad Bogdanovi, Vladana Vukojevi, Anne-Brita Knapskog
Summary: In this small pilot study, there was no association between serum nanoplaques and serum cytokines in patients assessed at a memory clinic. This suggests that serum nanoplaque levels cannot be used to differentiate clinical AD patients from non-AD patients in this unselected memory clinic cohort.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Ulrika Nordstrom, Lisa Lang, Elaheh Ekhtiari Bidhendi, Per Zetterstroem, Mikael Oliveberg, Jens Danielsson, Peter M. Andersen, Stefan L. Marklund
Summary: This study identified two hSOD1 aggregate strains that can spread and cause fatal paralysis in adult transgenic mice. The spreading of these aggregates could be a primary disease mechanism in SOD1-induced ALS. The structure and amount of aggregates formed varied between different hSOD1 mutants and different cell lines. It is suggested that pathogenesis and therapeutic development should be conducted in models that replicate aggregate structures forming in the central nervous system.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Eloy Vallina Estrada, Nannan Zhang, Hakan Wennerstrom, Jens Danielsson, Mikael Oliveberg
Summary: A striking feature of nucleic acids and lipid membranes is that they all carry net negative charge and so is true for the majority of intracellular proteins. It is suggested that the role of this negative charge is to assure a basal intermolecular repulsion that keeps the cytosolic content suitably 'fluid' for function. We focus in this review on the experimental, theoretical and genetic findings which serve to underpin this idea and the new questions they raise.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Mia L. Abramsson, Cagla Sahin, Jonathan T. S. Hopper, Rui M. M. Branca, Jens Danielsson, Mingming Xu, Shane A. Chandler, Nicklas Osterlund, Leopold L. Ilag, Axel Leppert, Joana Costeira-Paulo, Lisa Lang, Kaare Teilum, Arthur Laganowsky, Justin L. P. Benesch, Mikael Oliveberg, Carol Robinson, Erik G. Marklund, Timothy M. Allison, Jakob R. Winther, Michael Landreh
Summary: The presence of ionizable side chains in proteins affect their charging under native conditions, with preferential protonation sites. Absence of ionizable side chains results in similar charge state distributions under native-like and denaturing conditions, while an excess of ionizable side chains effectively modulates protein ion stability.