Article
Biochemistry & Molecular Biology
Lei Gu, Zhefeng Guo
Summary: The formation of A beta oligomers and fibrils is crucial in Alzheimer's disease pathogenesis. A beta 42 and A beta 40 interact with each other influencing their aggregation, and A beta 40 has been shown to reduce plaque pathology in mouse models. The study suggests that A beta 42 and A beta 40 can form mixed oligomers with direct molecular interactions.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(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)
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
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.
Review
Biochemistry & Molecular Biology
Nicolas Papadopoulos, Nuria Suelves, Florian Perrin, Devkee M. Vadukul, Celine Vrancx, Stefan N. Constantinescu, Pascal Kienlen-Campard
Summary: Most neurodegenerative diseases are characterized by protein folding disorders, such as Alzheimer's disease. These diseases lead to the appearance of protein aggregates in vulnerable regions of the nervous system, which progressively spread through the neuronal network. Alzheimer's disease is characterized by neurofibrillary tangles composed of tau proteins and senile plaques composed of amyloid peptides. Understanding the structural determinants of the precursor protein APP and the formation of different A beta aggregates is crucial in deciphering the pathological conformational changes and mechanisms underlying amyloid fibril formation.
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
Kenjiro Ono, Takahiro Watanabe-Nakayama
Summary: Alzheimer's disease is a common age-related neurodegenerative disorder characterized by plaques composed of amyloid beta-protein and neurofibrillary tangles of tau protein in the brain. Genetic studies have suggested that the misfolding and aggregation of Aβ molecules play a critical role in the pathogenesis of AD. Recent combination studies using NMR and cryo-EM have provided detailed information on the aggregation process and structural polymorphism of Aβ fibrils.
NEUROCHEMISTRY INTERNATIONAL
(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)
Review
Biochemistry & Molecular Biology
Phuong H. Nguyen, Philippe Derreumaux
Summary: The interactions between amyloid proteins and membranes have been extensively studied. Recent simulations have focused on the adsorption and insertion modes of amyloid-beta and tau proteins in membranes, aiming to design drugs that target the transient oligomers in Alzheimer's disease.
Article
Engineering, Chemical
Wei Liu, Xueting Sun, Xiaoyan Dong, Yan Sun
Summary: The chiral influence of peptide inhibitors on Aβ fibrillogenesis and cytotoxicity was investigated in this study. It was found that the D-enantiomer exhibited stronger inhibition effect on Aβ self-assembly compared to the L-enantiomer, with significant differences in their reaction.
CHINESE JOURNAL OF CHEMICAL ENGINEERING
(2022)
Article
Biochemistry & Molecular Biology
Panagiotis M. Spatharas, Georgia I. Nasi, Paraskevi L. Tsiolaki, Marilena K. Theodoropoulou, Nikos C. Papandreou, Andreas Hoenger, Ioannis P. Trougakos, Vassiliki A. Iconomidou
Summary: Clusterin is identified as a glycoprotein involved in amyloid formation and has aggregation-prone regions that can form amyloid-like fibrils while also inhibiting amyloid-beta fibril formation. These findings suggest a potential role of clusterin in the molecular mechanism of inhibiting amyloid formation and indicate a possible involvement of molecular chaperones with amyloidogenic properties in regulating amyloid formation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
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)
Review
Biochemistry & Molecular Biology
Yijing Tang, Dong Zhang, Xiong Gong, Jie Zheng
Summary: This article primarily discusses and summarizes the mechanistic causes of Alzheimer's disease (AD). Different mechanisms of AD could potentially work together to initiate, trigger, and promote the onset and development of the disease. Some of these mechanisms are also applicable to other amyloid diseases, explaining the pathogenesis and pathology spreading among these diseases.
BIOPHYSICAL CHEMISTRY
(2022)
Review
Chemistry, Inorganic & Nuclear
Yunjie Xu, Hao Xiong, Bin Zhang, Injun Lee, Jianlei Xie, Mingle Li, Han Zhang, Jong Seung Kim
Summary: Alzheimer's disease is a common form of dementia that is closely related to the aggregation of Aβ and Tau proteins in the brain, resulting in memory and learning deficits. Photodynamic therapy has emerged as a promising alternative for Alzheimer's treatment by using photon-triggered reactive oxygen species to intervene in the protein aggregations. This review summarizes the principles of photodynamic therapy, the state-of-the-art photodynamic molecules/photo-nanomedicine, and the pros and cons of this therapy, while providing suggestions for overcoming challenges in this field.
COORDINATION CHEMISTRY REVIEWS
(2022)
