Review
Biochemistry & Molecular Biology
Greta Elovsson, Liza Bergkvist, Ann-Christin Brorsson
Summary: Alzheimer's disease is a neurological disorder associated with proteotoxic events caused by the misfolding and aggregation of the amyloid-beta peptide. Drosophila melanogaster is utilized as a model organism to study the proteotoxicity of the amyloid-beta peptide and screen for drug candidates, which may provide insights into disease progression and potential treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Chemistry, Inorganic & Nuclear
Jun Li, Wang Liao, Dongqing Huang, Meitong Ou, Tongkai Chen, Xinlu Wang, Ruiyue Zhao, Lingyan Zhang, Lin Mei, Jun Liu, Ping Luan
Summary: Alzheimer's disease is a common central neurodegenerative disorder characterized by behavioral disturbance and progressive cognitive impairment. Accumulation of soluble oligomers and amyloid plaques outside nerve cells are crucial in its development. Advanced strategies for detecting and modulating amyloid beta (A beta) in diagnosis and treatment include the use of large-scale apparatus and novel devices, as well as therapeutic agents and nanomaterials.
COORDINATION CHEMISTRY REVIEWS
(2023)
Review
Medicine, Research & Experimental
Yan Zheng, Limin Zhang, Jinge Zhao, Lingyun Li, Minxuan Wang, Peifeng Gao, Qing Wang, Xiaoling Zhang, Weizhi Wang
Summary: Alzheimer's disease is an irreversible neurodegenerative disease with challenges in early diagnosis and treatment. The 3-β amyloid protein is an important biomarker, and aptamers play a crucial role in AD theranostics.
Article
Neurosciences
Tsuyoshi Hamaguchi, Jee Hee Kim, Akane Hasegawa, Ritsuko Goto, Kenji Sakai, Kenjiro Ono, Yoshinori Itoh, Masahito Yamada
Summary: The study found that exogenous A beta seeds from different A beta pathologies induced A beta deposition in the blood vessels rather than the brain parenchyma, which might be the predominant feature of A beta pathology in iatrogenic transmission cases; Contamination of brain tissues from patients with little A beta pathology could lead to iatrogenic transmission of A beta pathology, emphasizing the urgent need for the development of inactivation methods to prevent such transmission.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Zhongju Ye, Zhao-Jun Yan, Chenhong Zhang, Jun-Li Hou, Shijing Yue, Lehui Xiao
Summary: Anti-A beta therapy has been the main focus in clinical trials for AD prevention and treatment. This study introduced a new strategy using a charged tubular supramolecule to suppress A beta fibrillation, showing efficient inhibition of A beta(40) fibrillation by CTS-A at a very low inhibitor:peptide molar ratio (1:10) and a reduced cytotoxic effect of A beta peptides post-inhibition or disaggregation. The organized supramolecular structure enhances amyloid fibrillar modulation, offering a new approach for AD treatment using supramolecules.
Article
Medicine, Research & Experimental
Eunbi Cho, Kumju Youn, Huiyoung Kwon, Jieun Jeon, Wan-Seob Cho, Se Jin Park, Seung Hwan Son, Dae Sik Jang, Chan Young Shin, Minho Moon, Mira Jun, Nam-Jung Kim, Dong Hyun Kim
Summary: This study investigated the effects of eugenitol in an AD mouse model and found that it inhibits the formation of A beta plaques and reduces neuronal cell death. In silico docking simulation showed that eugenitol may interact with A beta monomers and fibrils.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Chemistry, Medicinal
Angelo Santoro, Manuela Grimaldi, Michela Buonocore, Ilaria Stillitano, Anna Maria D'Ursi
Summary: This study utilized NMR to analyze the conformational transition of A beta(1-42) in 50/50 HFIP/water, revealing unexpected routes in the evolution from helical to beta-sheet structures. Molecular dynamics simulations confirmed that the structural model calculated in this study is a starting point for amyloid fibrils formation.
Article
Biochemistry & Molecular Biology
Yasuteru Inoue, Masayoshi Tasaki, Teruaki Masuda, Yohei Misumi, Toshiya Nomura, Yukio Ando, Mitsuharu Ueda
Summary: In this study, the researchers found that α-enolase (ENO1) can interact with amyloid beta (Aβ) and inhibit its fibril formation. They also demonstrated that ENO1 can disrupt Aβ fibrils and weaken their cytotoxic effects by degrading Aβ peptides. Additionally, infusion of ENO1 into mouse brains reduced cerebrovascular Aβ deposits and improved cognitive impairment. These findings suggest that ENO1 may be a therapeutic target in cerebral amyloid angiopathy (CAA).
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Tuan D. Samdin, Chelsea R. Jones, Gretchen Guaglianone, Adam G. Kreutzer, J. Alfredo Freites, Michal Wierzbicki, James S. Nowick
Summary: This study investigates the arrangement, assembly, and function of beta-hairpins formed by the beta-amyloid peptide Aβ in oligomers. By synthesizing beta-hairpin peptides and conducting various experiments, the structure and function of the oligomers were revealed, and their relationship with membrane disruption and cell apoptosis was explored.
Article
Chemistry, Physical
Sauradipta Banerjee
Summary: Protein glycation, induced by a-dicarbonyl compound glyoxal in diabetic conditions, results in the formation of advanced glycation end products (AGEs) and structural alteration in proteins. The study on myoglobin incubated with glyoxal for 30 days revealed aggregation with amyloidal features and modification of specific residues to AGE adducts. This research provides insight into the mechanisms of AGE-induced protein modification and subsequent conformational disorders.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Biochemistry & Molecular Biology
Yan Wang, Meiling Lian, Xiaoyu Xiu, Zhiwen Zhang, Liping Song, Shengzhou Wu
Summary: This study found that Dicer1 expression mediated amyloid peptide clearance by increasing APOE and blocking B2 RNA-mediated APOE mRNA degradation, leading to improved spatial memory in an animal model of Alzheimer's disease.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
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
Biochemistry & Molecular Biology
Siddhartha Banerjee, Divya Baghel, Ana Pacheco de Oliveira, Ayanjeet Ghosh
Summary: This study used nanoscale AFM-IR spectroscopy to investigate the structure of Aβ oligomers and fibrils. It found that the main effect of beta-carotene is not to inhibit fibril formation, but to alter the secondary structure of the fibrils and promote fibrils that lack the characteristic ordered beta structure.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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
Chemistry, Multidisciplinary
Saida Majdoub, Zoltan Garda, Alexandre C. Oliveira, Inga Relich, Agnes Pallier, Sara Lacerda, Christelle Hureau, Carlos F. G. C. Geraldes, Jean-Francois Morfin, Eva Toth
Summary: Metal chelates targeted to amyloid peptides show promising nanomolar affinities for both A beta(1-40) and amylin when separated with a hydrophobic linker. The binding affinity of GdL complexes to A beta(1-40) or amylin varies with concentration and micellar aggregation state, affecting peptide aggregation kinetics. Ex vivo biodistribution experiments using In-111 labeled analogues in healthy mice suggest potential for amylin imaging in diabetic animals.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Hsiu-Fang Fan, Wen-Ling Chen, Yan-Zhow Chen, Jian-Wei Huang, Yu-Xin Shen
Summary: This study demonstrates that the abnormal accumulation of alpha-Syn protein in human brain cells is a pathological feature of Parkinson's disease. There are differences in oligomer formation and intracellular interactions between familial Parkinson's disease mutants and C-terminal alpha-Syn truncations.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
I-Ching Hsieh, Ting-Wei Chen, Ya-Ping Chuang, Yun-Ju Lai, Ling-Hsien Tu
Summary: This study investigates the aggregation of human calcitonin (hCT) and identifies Tyr12 as a key residue in regulating hCT aggregation. By modifying Tyr12, anti-aggregation variants of hCT were successfully developed.
Article
Biochemistry & Molecular Biology
Ying-Shuang Chang, Chih-Lung Lin, Chu-Wan Lee, Han-Chen Lin, Yi-Ting Wu, Yao-Hsiang Shih
Summary: This study investigates the effect of running exercise on 2K1C-induced hypertension in mice. The results show that running exercise improves spatial memory and neurogenesis impairment, normalizes RAS activity, and reduces blood-brain barrier leakage, indicating its potential in preventing hypertension-induced brain impairment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Plant Sciences
Wu-Fu Chen, Yao-Hsiang Shih, Hsuan-Chih Liu, Cheng- Cheng, Chi- Chang, Chung-Yi Chen, In-Pin Lin, Mei-Ying Lin, Chien-Hsing Lee
Summary: The study investigated the anti-inflammatory and antioxidant effects of flavonoid 6-methoxyflavone (6-MeOF) in microglia-mediated neuroinflammation. The results demonstrated that 6-MeOF reduced the expression of pro-inflammatory mediators, inhibited the activation of NF-Kappa B and MAPK signaling pathways, decreased the levels of reactive oxygen species (ROS), and induced the expression of antioxidant enzymes. Furthermore, 6-MeOF prevented the proliferation of microglia. These findings suggest that 6-MeOF has the potential to be used as a therapeutic agent for neuroinflammatory disorders.
Article
Chemistry, Multidisciplinary
Cai-Ling Shen, Yu-Hsuan Wu, Ting-Hao Zhang, Ling-Hsien Tu
Summary: More than 30 human peptides or proteins have been found to form amyloid fibrils, which are associated with various human diseases. However, there is currently no cure for amyloidosis. In this study, iron oxide nanoparticles were used to inhibit the aggregation of human calcitonin (hCT) and dissociate preformed amyloid fibrils, offering a potential therapeutic strategy for amyloidosis treatment.
Article
Biochemistry & Molecular Biology
Yu-Hao Lin, Yao-Hsiang Shih, Ye Vone Yap, Yen-Wei Chen, Hsiang-Lin Kuo, Tsung-Yun Liu, Li-Jin Hsu, Yu-Min Kuo, Nan-Shan Chang
Summary: When WWOX is downregulated in middle age, protein aggregation occurs and lasts for more than 30 years, leading to the development of Alzheimer's disease. Treatment with neurotoxin MPP+ results in the upregulation and aggregation of TPC6A Delta, which is a common initiator for both Alzheimer's disease and Parkinson's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Hao-Han Pang, Chiung-Yin Huang, Pin-Yuan Chen, Nan-Si Li, Ying-Pei Hsu, Jan-Kai Wu, Hsiu-Fang Fan, Kuo-Chen Wei, Hung-Wei Yang
Summary: Since GBMs are radioresistant malignancies and most GBM recurrences occur in radiotherapy, increasing the effectiveness of radiotherapy by gene-silencing has recently attracted attention. However, the difficulty in precisely tuning the composition and RNA loading in nanoparticles leads to batch-to-batch variations of RNA therapeutics, thus significantly restricting their clinical translation. In this study, bioengineered bacteriophage Q beta particles with a designed broccoli light-up three-way junction (b-3WJ) RNA scaffold were used for gene silencing in radioresistant GBM cells.
Article
Engineering, Biomedical
Bo-Wen Lin, Pao-Yen Lin, Yao-Hsiang Shih, Cheng-Lin Wu, Yeng-Ting Wu, Meei Jyh Jiang
Summary: The study aims to identify the role of turbulent components of blood flow in promoting aortic lumen dilatation. Moderate coarctation of the porcine abdominal aorta was induced to create overt flow turbulence and lead to dilatation. A new metric, fluctuation intensity (FI), was proposed to measure turbulent fluctuations of pulsatile aortic flow. Analysis revealed that high-intensity, high-frequency components of blood flow fluctuations induced by coarctation promote elastic lamella degradation and aortic lumen dilatation. The proposed metric, HFFI, was found to be a useful predictor of post-stenotic dilatation (PSD).
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
(2023)
Review
Chemistry, Multidisciplinary
Hsiu-Fang Fan
Summary: Single-molecule techniques are powerful tools to investigate protein-DNA interactions that are challenging to study using conventional biochemical techniques. By using single-molecule tethered particle motion, we have studied various protein-DNA interactions and obtained valuable information about homologous recombination, site-specific recombination, DNA packaging, and nucleosome remodeling processes.
JOURNAL OF THE CHINESE CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Ya-Ping Chuang, Yu-Pei Chang, Ling-Hsien Tu
Summary: The aggregation of proteins or peptides greatly limits their bioavailability, making it difficult to inhibit using small molecules or biocompatible materials. However, a previous study found that modifying certain residues in human calcitonin (hCT) can effectively suppress peptide aggregation. The modified hCT, known as double mutant hCT (DM hCT), acts as a good inhibitor and is biologically active in interacting with the calcitonin receptor. Creating peptide fragments based on the DM hCT sequence further revealed that the formation of a helix structure may contribute to its inhibitory effect.
Article
Nanoscience & Nanotechnology
Yu -Han Su, Han-Chen Lin, Hsing-Yen Li, Chih-Hsuan Lien, Yao-Hsiang Shih, Chian -Hui Lai
Summary: The aim of this study was to develop a carbohydrate silica nanocomposite, M-mDOX@SiO2, which can specifically target cancer cells and release the drug doxorubicin (DOX) specifically in an acidic tumor microenvironment (TME). The synthesized M-mDOX@SiO2 demonstrated high antitumor efficacy, making it a promising drug delivery carrier.
ACS APPLIED NANO MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Chen-Tsen Yeh, Han-Wen Chang, Wen-Hsin Hsu, Shing-Jong Huang, Meng-Hsin Wu, Ling-Hsien Tu, Ming-Che Lee, Jerry Chun Chung Chan
Summary: In this study, the structures and dynamics of A beta(40) oligomers of different sizes (10 nm and 23 nm) were compared for the first time using solid-state NMR. Chemical shift data suggest that the conformation and/or chemical environments of residues from K16 to K28 differ between the 10-nm and 23-nm oligomers. The 10-nm oligomers were found to be more cytotoxic, with more dynamic molecular motion of the sidechain of its charged residue K16. Interestingly, residue A21 exhibited unusually high structural rigidity. These findings raise the intriguing possibility that the cytotoxicity of A beta(40) oligomers could be correlated to the motional dynamics of the sidechains.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Nanoscience & Nanotechnology
Yu-Hsuan Wu, Yu-Pei Chang, Chia-Chien Hsu, Yi-Lun Chen, Pin-Han Lin, Ting-Wei Hsu, Wei-Min Liu, Yun-Ju Lai, Mei-Yi Liao, Ling-Hsien Tu
Summary: In this study, iron-oxide nanoparticles coated with porphyrin derivatives, Fe3O4-Chl/Fe and Fe3O4-Chl/Cu, were synthesized and used to stabilize and influence the aggregation of human calcitonin (hCT). The formation of hCT amyloid fibrils was monitored using a fluorescent probe. These findings can contribute to the development of hCT drug formulation.
ACS APPLIED NANO MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Han-Wen Chang, Ho- Ma, Yi-Shan Wu, Ming-Che Lee, Eric Chung-Yueh Yuan, Shing-Jong Huang, Yu-Sheng Cheng, Meng-Hsin Wu, Ling-Hsien Tu, Jerry Chun Chung Chan
Summary: This study successfully prepared high molecular-weight oligomeric aggregates of A beta with uniform size and monomorphic structure by incubating A beta peptides in reverse micelles. The A beta Os-40 adopted the structural motif of beta-loop-beta and the A beta Os-42 accelerated the fibrillization of A beta(40) monomers. Cross-seeding experiments showed that A beta Os-42 had an impact on the chemical states of certain residues in A beta Os-40.