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The accumulation of protein aggregates is the hallmark of many neurodegenerative diseases. The dysregulation of protein homeostasis (or proteostasis) caused by acute proteotoxic stresses or chronic expression of mutant proteins can lead to protein aggregation. Protein aggregates can interfere with a variety of cellular biological processes and consume factors essential for maintaining proteostasis, leading to a further imbalance of proteostasis and further accumulation of protein aggregates, creating a vicious cycle that ultimately leads to aging and the progression of age-related neurodegenerative diseases. Over the long course of evolution, eukaryotic cells have evolved a variety of mechanisms to rescue or eliminate aggregated proteins. Here, we will briefly review the composition and causes of protein aggregation in mammalian cells, systematically summarize the role of protein aggregates in the organisms, and further highlight some of the clearance mechanisms of protein aggregates. Finally, we will discuss potential therapeutic strategies that target protein aggregates in the treatment of aging and age-related neurodegenerative diseases.
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http://dx.doi.org/10.3390/ijms24108593 | DOI Listing |
Biomed Pharmacother
September 2025
Department of Biomedical Sciences, Institute of Health, Jimma University, Jimma 378, Ethiopia; Division of Research & Development, Lovely Professional University, Phagwara 144411, India. Electronic address:
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by cognitive decline and the accumulation of misfolded proteins, including amyloid-beta and hyperphosphorylated tau, which impair neuronal function and promote cell death. These misfolded proteins disrupt proteostasis by forming toxic aggregates that exacerbate disease progression. Molecular chaperones, such as heat shock proteins, actively maintain protein homeostasis by assisting in proper folding, preventing aggregation, and promoting the clearance of misfolded proteins.
View Article and Find Full Text PDFNeurobiol Aging
September 2025
O-Force Co., Ltd., 3454 Irino Kuroshio-cho, Hata-gun, Kochi 789-1931, Japan; Department of Pharmacology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan. Electronic address:
Due to the growing number of Alzheimer's disease (AD) patients, new drugs are urgently required. A synthetic nonapeptide, JAL-TA9 (YKGSGFRMI), derived from Transducer of ErbB-2.1 (Tob1) protein, cleaves amyloid β (Aβ) 42 with serine protease-like activity.
View Article and Find Full Text PDFISME J
September 2025
Department of Functional and Evolutionary Ecology, Archaea Biology and Ecogenomics Unit, University of Vienna, Djerassiplatz 1, 1030 Vienna, Austria.
Although ammonia-oxidizing archaea (AOA) are globally distributed in nature, growth in biofilms has been relatively little explored. Here we investigated six representatives of three different terrestrial and marine clades of AOA in a longitudinal and quantitative study for their ability to form biofilm, and studied gene expression patterns of three representatives. Although all strains grew on a solid surface, soil strains of the genera Nitrosocosmicus and Nitrososphaera exhibited the highest capacity for biofilm formation.
View Article and Find Full Text PDFInt J Biol Macromol
September 2025
Institute of Cytology Russian Academy of Sciences, St. Petersburg, Russia; Laboratory of structural dynamics, stability and folding of proteins, Institute of Cytology Russian Academy of Sciences, 4 Tikhoretsky ave., 194064, St. Petersburg, Russia. Electronic address:
Growing evidence links gut microbiota to neurodegenerative diseases, yet direct molecular interactions between bacterial and host amyloid proteins remain incompletely understood. Bacterial amyloids represent an understudied yet potentially critical component of gut-brain communication in neurodegeneration. Here, we provide the first investigation of whether amyloids formed by outer membrane proteins (OMPs) of enterobacteria can modulate neurodegeneration-associated protein aggregation.
View Article and Find Full Text PDFPLoS One
September 2025
Department of Chemistry, University of California, Irvine, California, United States of America.
Anti-Aβ antibodies are important tools for identifying structural features of aggregates of the Aβ peptide and are used in many aspects of Alzheimer's disease (AD) research. Our laboratory recently reported the generation of a polyclonal antibody, pAb2AT-L, that is moderately selective for oligomeric Aβ over monomeric and fibrillar Aβ and recognizes the diffuse peripheries of Aβ plaques in AD brain tissue but does not recognize the dense fibrillar plaque cores. This antibody was generated against 2AT-L, a structurally defined Aβ oligomer mimic composed of three Aβ-derived β-hairpins arranged in a triangular fashion and covalently stabilized with three disulfide bonds.
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