Article
Biochemistry & Molecular Biology
Jiai Hua, Feng Wang, Xueman Wei, Yuxin Qin, Jiameng Lian, Jianhong Wu, Pengtao Ma, Xiang Ma
Summary: A nanoscale manganese-substituted polyphosphomolybdate (MnPM) was synthesized to modulate the β-sheet rich conformation of A beta aggregates, reduce the formation of toxic species, and eliminate free radicals produced by Cu2+-A beta aggregates. MnPM demonstrated the ability to inhibit cytotoxicity and protect synapses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Nazaret Gamez, Javiera Bravo-Alegria, Yumeng Huang, Nelson Perez-Urrutia, Deepa Dongarwar, Claudio Soto, Rodrigo Morales
Summary: Extensive experimental and human-derived evidence suggests that misfolded A beta particles spread similarly to infectious prions. Administration of A beta seeds accelerates brain amyloidosis. Injection of A beta seeds in the tongue accelerates the appearance of plaques, while extra-nasal exposure increases amyloid pathology in the olfactory bulb. The results suggest that A beta seeds can be transported to the brain by retrograde axonal transport, and research in this direction may be relevant in understanding disease mechanisms, diagnosis, and iatrogenic transmission risk evaluation.
Review
Biochemistry & Molecular Biology
Chen Ma, Fenfang Hong, Shulong Yang
Summary: This review provides an overview of the amyloid hypothesis of Alzheimer's disease, emphasizing the key role of amyloid beta protein in AD. The review also discusses the process of amyloid formation, autophagy, cerebral blood flow, and the detailed pathogenesis of amyloidosis.
Review
Biochemistry & Molecular Biology
Anna Kozell, Aleksei Solomonov, Ulyana Shimanovich
Summary: In the past, ultrasound and protein complexes were considered unrelated topics. However, recent studies have focused on the ability of ultrasound to induce chemical modifications on proteins, leading to changes in protein-protein interactions and self-assembly. Despite limited understanding of these phenomena, this review provides a comprehensive analysis of the role of ultrasound in protein complexation, with a specific focus on amyloid self-assembly relevant to neurodegenerative disorders.
Review
Neurosciences
Alessio Crestini, Francesca Santilli, Stefano Martellucci, Elena Carbone, Maurizio Sorice, Paola Piscopo, Vincenzo Mattei
Summary: Specific protein misfolding and aggregation are mechanisms underlying neurodegenerative diseases such as prion disease and Alzheimer's disease (AD). The misfolded proteins contribute to the pathological features of AD, including the formation of plaques and neurofibrillary tangles. The cellular prion protein (PrPC) has an important role in the pathogenesis of AD.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Tsuyoshi Hamaguchi, Kenjiro Ono, Masahito Yamada
Summary: Deposition of amyloid beta protein in the brain is a characteristic of Alzheimer's disease, which can be transmitted between individuals through a prion-like mechanism. Pathological studies have shown that patients with iatrogenic Creutzfeldt-Jakob disease, caused by medical procedures such as human growth hormone injection and dura mater graft, also have cerebral amyloid beta protein deposition. Additionally, young patients with cerebral amyloid angiopathy-related cerebral hemorrhage, who have undergone neurosurgeries with or without dura mater graft in early childhood, suggest that the transmission of cerebral amyloid beta protein pathology is often through amyloid angiopathy rather than parenchymal deposition.
NEUROCHEMICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Ruben Gomez-Gutierrez, Ujjayini Ghosh, Wai-Ming Yau, Nazaret Gamez, Katherine Do, Carlos Kramm, Hamid Shirani, Laura Vegas-Gomez, Jonathan Schulz, Ines Moreno-Gonzalez, Antonia Gutierrez, K. Peter R. Nilsson, Robert Tycko, Claudio Soto, Rodrigo Morales
Summary: The study examines the seeding properties of two structurally defined synthetic misfolded Aβ strains (2F and 3F) and their different pathological features, including aggregation rates, plaque formation, tropism to specific brain regions, recruitment of different Aβ peptides, and induction of microglial and astroglial responses. Moreover, the study analyzes the atomic-level characterization of purified Aβ polymorphs and provides relevant information on the pathological significance of misfolded Aβ strains.
Article
Chemistry, Applied
Laura Fitzner, Mario Hasler, Timon R. Heyn, Karin Schwarz, Julia Katharina Keppler
Summary: Unfolding, with or without acid hydrolysis, is necessary for the formation of functional amyloid or amyloid-like β-lactoglobulin aggregates induced by temperature treatment at pH 2-4. UVB radiation can be used as a conformational perturbing treatment to promote protein aggregation by destabilizing the protein structure. UV-treated BLG exhibited accelerated worm-like aggregation at pH 3.5 and decelerated fibril formation at pH 2. The UV-induced conformational destabilization enhanced the unfolding process during thermal treatment, favoring the formation of covalent and non-covalent intermolecular interactions and resulting in worm-like aggregates. Oxidative degradation of UV-treated BLG hindered peptide assembly by altering fibrillation-prone protein regions.
Article
Chemistry, Multidisciplinary
Xiaotong Wang, Rui Zhou, Xiaqin Sun, Jun Li, Jinxin Wang, Weihua Yue, Lifang Wang, Hesheng Liu, Yigong Shi, Dai Zhang
Summary: This study reveals the mechanism of GM1 in Aβ generation and provides evidence that decreasing GM1 levels represents a potential strategy in AD treatment. GM1 can lead to conformational change in the structure of γ-secretase and accelerate the cleavage of APP, leading to reduced plaque deposition and improved cognitive dysfunction in AD.
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
Fei Li, Lingjia Zhou, Xu Gao, Weiwei Ni, Jiabao Hu, Meicen Wu, Shouwang Chen, Jinsong Han, Jin Wu
Summary: This study developed a multichannel fluorescent tongue that can accurately detect the aggregation states of Alzheimer's disease through machine learning algorithm-based optimization.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Shon A. Levkovich, Sigal Rencus-Lazar, Ehud Gazit, Dana Laor Bar-Yosef
Summary: Protein misfolding and aggregation are linked to human diseases and aging, while microorganisms use prions as carriers of epigenetic information to drive phenotypic adaptations and encode molecular information. Recent microbial prion research has revealed the functional and structural diversity of these agents. A hypothesis regarding the existence of non-proteinaceous prion-like entities has been proposed in light of advancements in molecular self-assembly.
TRENDS IN BIOCHEMICAL SCIENCES
(2021)
Article
Chemistry, Physical
Siddhartha Banerjee, Ayanjeet Ghosh
Summary: The aggregation of tau protein plays a central role in neurodegenerative diseases, with the study revealing structural heterogeneities in tau aggregates associated with different diseases, as well as multiple fibrillar polymorphs within the same tau aggregate. Additionally, mature fibrils were found to contain significant amounts of antiparallel beta sheets. The research demonstrates the promise of using nanoscale infrared spectroscopy for spatially resolved investigation of protein aggregation.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Physical
Siddhartha Banerjee, Divya Baghel, Md Hasan Ul Iqbal, Ayanjeet Ghosh
Summary: Spontaneous aggregation of amyloid beta (Afi) proteins is a key pathological feature of Alzheimer's disease, but the structure of early-stage aggregates is not well understood. This study used atomic force microscopy-infrared nanospectroscopy to investigate the aggregation process of Afi 16-22 and found a structural transition from oligomers with parallel β-sheets to antiparallel fibrils.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Xin Chen, Santosh Pandit, Lei Shi, Vaishnavi Ravikumar, Julie Bonne Kohler, Ema Svetlicic, Zhejian Cao, Abhroop Garg, Dina Petranovic, Ivan Mijakovic
Summary: Alzheimer's disease is a common neurodegenerative disease characterized by the aggregation of misfolded amyloid-beta peptides in the brain. Graphene oxide nanoflakes have been found to effectively inhibit A beta aggregation in vitro. In this study using yeast as a model, it is shown that graphene oxide can penetrate yeast cells and reduce A beta 42 toxicity. The findings provide insights for designing graphene oxide-based therapies for attenuating cytotoxicity of A beta 42 and other misfolded proteins involved in neurodegenerative pathology.
ADVANCED FUNCTIONAL MATERIALS
(2023)