Article
Medicine, Research & Experimental
Julia Ring, Jelena Tadic, Selena Ristic, Michael Poglitsch, Martina Bergmann, Nemanja Radic, Dirk Mossmann, Yongtian Liang, Marta Maglione, Andrea Jerkovic, Roozbeh Hajiraissi, Marcel Hanke, Victoria Kuettner, Heimo Wolinski, Andreas Zimmermann, Lana Domuz Trifunovic, Leonie Mikolasch, Daiana N. Moretti, Filomena Broeskamp, Julia Westermayer, Claudia Abraham, Simon Schauer, Christopher Dammbrueck, Sebastian J. Hofer, Mahmoud Abdellatif, Guido Grundmeier, Guido Kroemer, Ralf J. Braun, Niklas Hansen, Cornelia Sommer, Mirjana Ninkovic, Sandra Seba, Patrick Rockenfeller, Friederike-Nora Voegtle, Joern Dengjel, Chris Meisinger, Adrian Keller, Stephan J. Sigrist, Tobias Eisenberg, Frank Madeo
Summary: In this study, the researchers used yeast and fruit fly models to investigate the role of HSP40 family member Ydj1 in Alzheimer's disease. They found that Ydj1 physically interacts with Abeta42, stabilizes Abeta42 oligomers, and facilitates their translocation to mitochondria, resulting in cell death and memory impairment.
EMBO MOLECULAR MEDICINE
(2022)
Article
Clinical Neurology
Ashvini Keshavan, Josef Pannee, Thomas K. Karikari, Juan Lantero Rodriguez, Nicholas J. Ashton, Jennifer M. Nicholas, David M. Cash, William Coath, Christopher A. Lane, Thomas D. Parker, Kirsty Lu, Sarah M. Buchanan, Sarah E. Keuss, Sarah-Naomi James, Heidi Murray-Smith, Andrew Wong, Anna Barnes, John C. Dickson, Amanda Heslegrave, Erik Portelius, Marcus Richards, Nick C. Fox, Henrik Zetterberg, Kaj Blennow, Jonathan M. Schott
Summary: The study compared three different blood-based techniques for identifying early stage Alzheimer's disease, with mass spectrometry plasma measures performing significantly better than other measures.
Article
Clinical Neurology
Ashvini Keshavan, Josef Pannee, Thomas K. Karikari, Juan Lantero Rodriguez, Nicholas J. Ashton, Jennifer M. Nicholas, David M. Cash, William Coath, Christopher A. Lane, Thomas D. Parker, Kirsty Lu, Sarah M. Buchanan, Sarah E. Keuss, Sarah-Naomi James, Heidi Murray-Smith, Andrew Wong, Anna Barnes, John C. Dickson, Amanda Heslegrave, Erik Portelius, Marcus Richards, Nick C. Fox, Henrik Zetterberg, Kaj Blennow, Jonathan M. Schott
Summary: The study compared three different blood-based techniques to detect amyloid PET positivity in dementia-free individuals, finding that mass spectrometry plasma measures performed significantly better than other measures, with higher sensitivity and specificity for detecting amyloid PET positivity.
Article
Multidisciplinary Sciences
Ming-Chyi Pai, Chau-Chung Wu, Yi-Chou Hou, Jiann-Shing Jeng, Sung-Chun Tang, Wei-Che Lin, Cheng-Hsien Lu, Ming-Jang Chiu, Ta-Fu Chen, Sui-Hing Yan, Chaur-Jong Hu, Shieh-Yueh Yang
Summary: Patients with comorbidities are at risk for neurodegeneration. A study found significantly higher levels of plasma A beta(1-42) and T-Tau in patients with poststroke, family history of Alzheimer's disease, diabetes, end-stage renal disease, and obstructive sleep apnea.
SCIENTIFIC REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Giacomo Siano, Chiara Falcicchia, Nicola Origlia, Antonino Cattaneo, Cristina Di Primio
Summary: Tau plays a central role in tauopathies by causing neurodegeneration through misfolding and aggregation of Tau protein, leading to synaptic dysfunction. Research has shown that Tau undergoes post-translational modifications at the onset of pathology, resulting in detachment from the cytoskeleton, aggregation into toxic oligomers, and disruption of synaptic homeostasis, ultimately leading to neuronal degeneration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Michele F. M. Sciacca, Irina Naletova, Maria Laura Giuffrida, Francesco Attanasio
Summary: Alzheimer's disease, characterized by the aggregation of amyloid beta protein (A beta), is a common form of dementia. The aggregation and toxicity of A beta are strongly influenced by metal ions and phospholipidic membranes, particularly Cu2+ ions. Currently, there are no available treatments for this disease, but multifunctional compounds that can inhibit A beta fibrillogenesis and prevent the formation of A beta:Cu2+ complexes are of great interest.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Geriatrics & Gerontology
Ingmar Skoog, Silke Kern, Jenna Najar, Rita Guerreiro, Jose Bras, Margda Waern, Henrik Zetterberg, Kaj Blennow, Anna Zettergren
Summary: This study found that genetic risk of AD beyond the APOE locus is associated with NfL in individuals without A beta 42 pathology, and with A beta 42 in APOE epsilon 4 carriers, suggesting these associations are driven by different mechanisms in cognitively healthy 70-year olds from the general population.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Li Wang, Kilho Eom, Taeyun Kwon
Summary: The study found that in the initial stage of aggregation process for both Aβ40 and Aβ42, multiple particles are formed which later self-assemble to form amyloid fibrils of different shapes. Different aggregation pathways of Aβ isoforms lead to amyloid fibrils with contrasting structures.
Article
Neurosciences
Antonio J. Figueira, Joana Saavedra, Isabel Cardoso, Claudio M. Gomes
Summary: Extracellular aggregation of the amyloid-beta 1-42 peptide is a major characteristic of Alzheimer's disease (AD), and recent studies have shown that the intermediate oligomers of amyloid-beta are more cytotoxic than mature fibrils. In this study, the researchers investigated how different chaperone multimers of S100B, a signaling protein increased in AD, influence the formation of amyloid-beta oligomers. It was found that dimeric S100B-Ca2+ C drastically decreased the rate of oligomerization and levels of amyloid-beta oligomers, while tetrameric apo-S100B inhibited both oligomerization and fibril elongation. These findings highlight the potential neuroprotective role of different S100B multimers in AD.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Kamlesh M. Makwana, Matthew P. Sarnowski, Jiayuan Miao, Yu-Shan Lin, Juan R. Del Valle
Summary: The study introduces a minimalist approach to mimic the aggregation-prone modules within tau, showing efficacy in inhibiting tau fibril formation through a series of experiments.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Hariharakrishnan Chidambaram, Subashchandrabose Chinnathambi
Summary: Alzheimer's disease is characterized by the accumulation of Tau protein in cells, and cysteine residues play a crucial role in this aggregation process. In this study, it was found that even cysteine mutant Tau can aggregate to form filaments under in-vitro conditions, although with a delayed aggregation compared to wild-type Tau.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Neurosciences
Zhongting Zhao, Zheng Li, Fangning Du, Yixin Wang, Yue Wu, Kah-leong Lim, Lin Li, Naidi Yang, Changmin Yu, Chengwu Zhang
Summary: Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Misfolding, aggregation, and abnormal degradation of proteins are believed to be key factors in the pathogenesis of PD. Heat shock protein 70 (Hsp70) and Parkin, an E3 ubiquitin ligase, have been found to play important roles in PD pathogenesis. This review focuses on the dysregulation of Hsp70 and Parkin, their interaction, and their potential therapeutic applications in PD.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Antonio J. Figueira, Guilherme G. Moreira, Joana Saavedra, Isabel Cardoso, Claudio M. Gomes
Summary: The hallmark of Alzheimer's disease (AD) includes the aggregation of amyloid-beta (A beta), tau, and neuroinflammation. In this study, the researchers found that S100B protein, which is upregulated in AD, can inhibit the aggregation of A beta 42, and this activity is dependent on Ca2+ binding. They also discovered that S100B exists in tetrameric form, and tetrameric S100B is more effective in inhibiting A beta 42 aggregation. These findings highlight the importance of S100B protein in regulating AD proteotoxicity.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Ziqi Zhang, Qiong Yuan, Meiqi Li, Benkai Bao, Yanli Tang
Summary: This study developed a new ratiometric fluorescence probe for sensitive recognition, effective inhibition, and detoxification of toxic amyloid beta protein (A beta) aggregates, showing potential for early diagnosis and treatment of neurodegenerative diseases.
Article
Multidisciplinary Sciences
Bailey A. Garcia H. Manriquez, Julia A. A. Papapanagiotou, Claire A. Strysick, Emily Green, Elise Kikis
Summary: The proteostasis network is crucial for maintaining proper protein synthesis, transport, folding, and degradation. Diseases like Huntington's disease and Alzheimer's disease are associated with a failure of the proteostasis network, leading to protein misfolding and aggregation. Exposure to air pollution has been shown to exacerbate symptoms of Alzheimer's disease and trigger the accumulation of misfolded protein. The study found that nano-sized particulate air pollution (nPM) increased protein aggregation in muscle cells and negatively impacted proteostasis, suggesting that nPM exposure may contribute to the progression of neurodegenerative diseases.