Review
Biochemistry & Molecular Biology
Jennifer Ramirez, Samantha X. Pancoe, Elizabeth Rhoades, E. James Petersson
Summary: This article investigates the effects of interactions between the small neuronal protein alpha-synuclein and lipids on aggregation. By analyzing a comprehensive collection of experimental data, the general trends of lipid structure influencing aggregation are identified, providing a resource for interpreting the effects of lipids on aggregation and potentially serving as inputs for computational models.
Article
Biochemistry & Molecular Biology
R. Kavya, Snehal Aouti, Sneha Jos, Thazhe Kootteri Prasad, K. N. Kumuda, Sruthi Unni, Balasundaram Padmanabhan, Neelagandan Kamariah, Sivaraman Padavattan, Rajeswara Babu Mythri
Summary: Alpha-synuclein aggregation, associated with Parkinson's disease, is driven by the region alpha Syn(36-42) and alpha Syn(1-12). Celastrol, one of the screened phytochemicals, exhibits high binding affinity with alpha Syn. NMR analysis confirms stable interactions between alpha Syn and celastrol, reducing alpha Syn aggregation, making celastrol a potential drug candidate for Parkinson's disease.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Chemistry, Multidisciplinary
Ryan Limbocker, Nunilo Cremades, Roberta Cascella, Peter M. Tessier, Michele Vendruscolo, Fabrizio Chiti
Summary: The misfolding and aggregation of peptides and proteins into amyloid aggregates is a common feature of various protein misfolding diseases, including Alzheimer's disease and Parkinson's disease. Misfolded protein oligomers, which can form intermediates in the fibril formation process or be released by mature fibrils, are increasingly recognized as central to the development of these diseases. Despite challenges in studying these oligomers, researchers have developed methods to produce stable and reproducible populations for experimentation. These tools have provided insights into the structural determinants of oligomer toxicity and potential therapeutic strategies.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Neurosciences
Antonio Dominguez-Meijide, Valeria Parrales, Eftychia Vasili, Florencia Gonzalez-Lizarraga, Annekatrin Konig, Diana F. Lazaro, Annie Lannuzel, Stephane Haik, Elaine Del Bel, Rosana Chehin, Rita Raisman-Vozari, Patrick P. Michel, Nicolas Bizat, Tiago Fleming Outeiro
Summary: Doxycycline shows neuroprotective effects by reducing and inhibiting the aggregation of α-synuclein, attenuating oxidative stress in cells, and may be an effective strategy against synucleinopathies such as Parkinson's disease.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Rafael Ramis, Joaquin Ortega-Castro, Bartolome Vilanova, Miquel Adrover, Juan Frau
Summary: Alpha-synuclein, an intrinsically disordered protein, is associated with Parkinson's disease and other neurodegenerative disorders. Metal cations play a crucial role in influencing the aggregation propensity of alpha-synuclein, either by directly binding to it or catalyzing the production of reactive oxygen species. Molecular dynamics simulations reveal that metal binding or methionine sulfoxidation alters the conformational preferences of alpha-synuclein, leading to changes in its aggregation propensity.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Multidisciplinary Sciences
Ryan P. McGlinchey, Xiaodan Ni, Jared A. Shadish, Jiansen Jiang, Jennifer C. Lee
Summary: The study demonstrates that C-terminal truncations can accelerate the aggregation of alpha-synuclein, while the role of N-terminal truncations remains unclear. The research found that N-terminal truncations modulated the aggregation kinetics and fibril morphologies of alpha-synuclein.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Pratibha Kumari, Dhiman Ghosh, Agathe Vanas, Yanick Fleischmann, Thomas Wiegand, Gunnar Jeschke, Roland Riek, Cedric Eichmann
Summary: This study investigated the interaction between monomeric alpha-Syn and its fibrillar form using NMR and electron paramagnetic resonance spectroscopy, revealing that intermolecular interactions reduce intramolecular contacts in monomeric alpha-Syn, leading to further unfolding of its intrinsically disordered states and critically contributing to the aggregation kinetics of alpha-Syn during secondary nucleation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Yoshitsugu Nakamura, Shigeki Arawaka, Hiroyasu Sato, Asuka Sasaki, Taro Shigekiyo, Kazue Takahata, Hiroko Tsunekawa, Takeo Kato
Summary: Inhibiting MAO-B enzymatic activity can facilitate the secretion of alpha-synuclein and delay protein aggregation and loss of dopaminergic neurons in Parkinson's disease models.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Cell Biology
Niharika Amireddy, Vandana Dulam, Shweta Kaul, Rajeswari Pakkiri, Shasi V. Kalivendi
Summary: Upregulation and aggregation of a-synuclein is a key factor in Parkinson's disease, and mitochondrial dysfunction is believed to be a contributing factor. The drug nitazoxanide has been found to enhance mitochondrial function and autophagy. This study demonstrates that nitazoxanide activates cellular autophagy and clears a-synuclein aggregates through mitochondrial uncoupling, AMPK activation, and JNK activation.
CELLULAR SIGNALLING
(2023)
Article
Chemistry, Physical
Daniel Klose, Sahithya Phani Babu Vemulapalli, Michal Richman, Safra Rudnick, Vered Aisha, Meital Abayev, Marina Chemerovski, Meital Shviro, David Zitoun, Katharina Majer, Nino Wili, Gil Goobes, Christian Griesinger, Gunnar Jeschke, Shai Rahimipour
Summary: The presence of metal ions such as Cu2+ can accelerate the self-assembly of pathogenic proteins, forming cytotoxic intermediates. The extent of structuring of these intermediates in the initial stage of fibril formation is largely unknown. In this study, it was found that Cu2+ can bind to a cyclic D,L-alpha-peptide, generating amyloid-like cross-beta-sheet structures. The concentration of Cu2+ can influence the formation of different polymorphs, transitioning from fibrillar structures to spherical particles. Cu2+ is coordinated by two histidines, similar to self-assembled peptides, indicating a perpetuated binding interface during Cu2+-driven oligomerization.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Multidisciplinary Sciences
Sabine M. Ulamec, Roberto Maya-Martinez, Emily J. Byrd, Katherine M. Dewison, Yong Xu, Leon F. Willis, Frank Sobott, George R. Heath, Patricija van Oosten Hawle, Vladimir L. Buchman, Sheena E. Radford, David J. Brockwell
Summary: In this study, the authors characterized the impact of amino acid substitution on alpha-synuclein aggregation. They found that residues 38 and 42 within the P1 region of alpha-synuclein influence amyloid formation.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Alimohammad Hojjatian, Anvesh K. R. Dasari, Urmi Sengupta, Dianne Taylor, Nadia Daneshparvar, Fatemeh Abbasi Yeganeh, Lucas Dillard, Brian Michael, Robert G. Grif, Mario J. Borgnia, Rakez Kayed, Kenneth A. Taylor, Kwang Hun Lim
Summary: Recent studies reveal that amyloid filaments extracted from human patients with different disease phenotypes show diverse molecular conformations, potentially influenced by cofactors in vivo. Additionally, the structural differences between ex vivo alpha-synuclein filaments and in vitro filaments suggest a role of cofactors in alpha-synuclein aggregation in vivo. The findings highlight the importance of further structural investigations into alpha-synuclein filaments formed in the presence of different cofactors to better understand the molecular basis of the disease phenotype.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Neurosciences
Hao Gu, Xiuli Yang, Xiaobo Mao, Enquan Xu, Chen Qi, Haibo Wang, Saurav Brahmachari, Bethany York, Manjari Sriparna, Amanda Li, Michael Chang, Pavan Patel, Valina L. Dawson, Ted M. Dawson
Summary: The depletion of Lag3 in transgenic mice carrying human alpha-syn A53T mutation significantly reduces insoluble alpha-syn aggregates, delays disease progression, improves behavioral deficits, and prolongs survival, indicating the contribution of Lag3 to the pathogenesis in this model.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Review
Pharmacology & Pharmacy
Md Ezazul Haque, Mahbuba Akther, Shofiul Azam, In-Su Kim, Yuxi Lin, Young-Ho Lee, Dong-Kug Choi
Summary: In Parkinson's disease, the aggregated alpha-synuclein in Lewy bodies and mitochondrial dysfunction play crucial roles in neurodegeneration, with interactions between aggregated alpha-synuclein and mitochondria potentially leading to neuronal loss, making it an emerging drug target for Parkinson's disease treatment.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
S. Jadavi, S. Dante, L. Civiero, M. Sandre, L. Bubacco, L. Tosatto, P. Bianchini, C. Canale, A. Diaspro
Summary: In a previous study, it was shown that the coexistence of different aggregation pathways of insulin and A beta peptides was due to suboptimal proteins labeling strategies. However, this phenomenon could not be considered valid for all molecular systems. In this study, the aggregation process of alpha-syn was investigated, and it was found that a specific labeling method could avoid labeling artifacts. These results highlight the importance of careful designing the labeling strategy for the molecular system under investigation.
Article
Electrochemistry
Pengyu Xu, Wolfgang Rheinheimer, Avanish Mishra, Shoumya Nandy Shuvo, Zhimin Qi, Haiyan Wang, Avinash M. Dongare, Lia A. Stanciu
Summary: The interface between cathode and electrolyte is a significant source of large interfacial resistance in solid-state batteries. Spark plasma sintering can densify electrolyte and electrodes in one step and shorten processing time. Interdiffusion between Ti4+/Co3+ at the interface was observed, leading to the formation of specific phases and high interface resistance.
Article
Nanoscience & Nanotechnology
Ana M. Ulloa, Nicholas Glassmaker, Muhammed R. Oduncu, Pengyu Xu, Alexander Wei, Mukerrem Cakmak, Lia Stanciu
Summary: A roll-to-roll manufactured electrochemical sensor has been developed for detecting nitroaromatic organophosphorus pesticides, with high sensing and manufacturing reproducibility. The sensor, based on a flexible, screenprinted silver electrode modified with graphene nanoplatelets and zirconia, showed advantageous electrocatalytic activity towards NOPPs, along with high sensitivity, selectivity, and stability. The enzymeless sensor demonstrated a rapid response time and noncomplex detection of NOPPs, with a detection limit as low as 1 mu M and a linear correlation between MP concentration and current response.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Biochemistry & Molecular Biology
Aswathy Chandran, Jean-Christophe Rochet
Summary: A novel assay using a photoconvertible fusion protein identified autophagy inducers that either alleviated or exacerbated neurotoxicity in different cellular models of amyotrophic lateral sclerosis, challenging the notion that autophagy stimulation can be used as a one-size-fits-all therapy for neurodegenerative diseases.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biophysics
Ana M. Ulloa-Gomez, Alec Lucas, Abbey Koneru, Amit Barui, Lia Stanciu
Summary: We have developed a novel aptasensor that can detect mercury (Hg2+) through both colorimetric and electrochemical methods. This device is portable, rapid, and versatile, and can detect Hg2+ down to 0.01 ppm. It shows high selectivity against other heavy metals and offers a dual detection platform with quantification and multiplexing capabilities.
BIOSENSORS & BIOELECTRONICS
(2023)
Article
Biophysics
Sandeep B. Somvanshi, Ana M. Ulloa, Min Zhao, Qiyue Liang, Amit Kumar Barui, Alec Lucas, K. M. Jadhav, Jan P. Allebach, Lia A. Stanciu
Summary: Foodborne pathogens are a major concern for public health globally. In this study, a novel paper-based microfluidic device was developed to simultaneously detect multiple foodborne bacteria. The device provides quantitative readings through image analysis and utilizes custom designed particles for signal enhancement and false results prevention. The results show linearity over a wide concentration range and high specificity, making this device suitable for on-site rapid screening of pathogenic bacteria in water and food products.
BIOSENSORS & BIOELECTRONICS
(2022)
Article
Chemistry, Multidisciplinary
Winston Yenyu Chen, Connor Daniel Sullivan, Sz-Nian Lai, Chao-Chun Yen, Xiaofan Jiang, Dimitrios Peroulis, Lia A. Stanciu
Summary: Two-dimensional transition-metal carbides and nitrides (MXenes) have shown promising sensing capabilities, but suffer from weak gas-molecule adsorption limiting their sensitivity and selectivity. Through Au-decoration, MXenes exhibit enhanced response and selectivity in detecting VOCs, especially formaldehyde, with a low detection limit of 92 ppb at room temperature. Au-Ti3C2Tx sensors offer reliable gas response, low noise level, ultrahigh signal-to-noise ratio, high selectivity, and parts per billion level detection of formaldehyde.
Article
Biophysics
Ana M. Ulloa-Gomez, Alejandra Agredo, Alec Lucas, Sandeep B. Somvanshi, Lia Stanciu
Summary: We developed an aptasensing platform for the detection of cTnT in the immediate and early phases of AMI. The platform uses a microfluidic paper-based analytical device modified with gold-decorated polystyrene microparticles functionalized with a highly specific cTnT aptamer. The platform showed high selectivity and stability, and provides a label-free, smartphone-based detection method with shorter processing time compared to traditional methods.
BIOSENSORS & BIOELECTRONICS
(2023)
Article
Biochemical Research Methods
Der-Shyang Kao, Yanyan Du, Andrew G. DeMarco, Sehong Min, Mark C. Hall, Jean-Christophe Rochet, W. Andy Tao
Summary: Hyperphosphorylation of the microtubule-associated protein Tau is a major characteristic of Alzheimer's disease and other tauopathies. This study identified 59 Tau kinases, including 23 known kinases and 36 novel candidates, using fluorescence complementation mass spectrometry. Four candidate kinases, OXSR1, DAPK2, CSK, and ZAP70, were found to phosphorylate Tau in vitro and increase its phosphorylation in human neuroglioma cells. This research provides new opportunities for developing therapeutic strategies for Alzheimer's disease.
MOLECULAR & CELLULAR PROTEOMICS
(2022)
Article
Neurosciences
Pablo Martinez, Henika Patel, Yanwen You, Nur Jury, Abigail Perkins, Audrey Lee-Gosselin, Xavier Taylor, Yingjian You, Gonzalo Viana Di Prisco, Xiaoqing Huang, Sayan Dutta, Aruna B. Wijeratne, Javier Redding-Ochoa, Syed Salman Shahid, Juan F. Codocedo, Sehong Min, Gary E. Landreth, Amber L. Mosley, Yu-Chien Wu, David L. McKinzie, Jean-Christophe Rochet, Jie Zhang, Brady K. Atwood, Juan Troncoso, Cristian A. Lasagna-Reeves
Summary: This study identified the interaction between the presynaptic protein Bassoon and the tau seed, enhancing its stability and promoting tau toxicity and spreading. Decreasing the expression level of Bassoon can reduce tau propagation and overall disease pathology, improving synaptic and behavioral impairments, and reducing brain atrophy.
NATURE NEUROSCIENCE
(2022)
Article
Nanoscience & Nanotechnology
Ulisses Heredia-Rivera, Venkat Kasi, Akshay Krishnakumar, Sachin Kadian, Amit Kumar Barui, Zihao He, Haiyan Wang, Lia Stanciu, Rahim Rahimi
Summary: Cold atmospheric plasma-assisted deposition technology is a solvent-free and scalable method for in situ polymerization and direct deposition of conductive polypyrrole-silver nanocomposites. By adjusting the precursor composition, PPy-Ag nanocomposite films with tunable degrees of polymerization and Ag nanoparticle loading can be fabricated.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Editorial Material
Biochemistry & Molecular Biology
Jean-Christophe Rochet
Article
Cell Biology
Audrey Lee-Gosselin, Nur Jury-Garfe, Yanwen You, Luke Dabin, Disha Soni, Sayan Dutta, Jean-Christophe Rochet, Jungsu Kim, Adrian L. Oblak, Cristian A. Lasagna-Reeves
Summary: The study investigated the effects of TREM2 deficiency on tau spreading using a mouse model and found that Trem2(-/-) mice showed attenuated tau pathology in multiple brain regions along with decreased microglial density. The reduced TREM2 signaling impaired microglia activation and their contribution to tau spreading. However, caution should be exercised before targeting TREM2 as a therapeutic entry point for Alzheimer's disease until its involvement in tau aggregation and propagation is better understood.
Article
Biochemistry & Molecular Biology
Mitali A. Tambe, Aurelie de Rus Jacquet, Katherine E. Strathearn, Jennifer A. Hensel, Bryce D. Colon, Aswathy Chandran, Gad G. Yousef, Mary H. Grace, Mario G. Ferruzzi, Qingli Wu, James E. Simon, Mary Ann Lila, Jean-Christophe Rochet
Summary: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra region of the brain. Anthocyanin (ANC) intake has been associated with a reduced risk of PD. This study found that botanical extracts enriched with ANC and other polyphenols could protect against the death of dopaminergic neurons caused by PD-related toxins, such as paraquat (PQ) and rotenone. These extracts activated cellular antioxidant mechanisms and alleviated mitochondrial dysfunction, suggesting their potential to slow neurodegeneration in individuals exposed to PQ or rotenone.
Article
Biochemistry & Molecular Biology
Aurelie de Rus Jacquet, Abeje Ambaw, Mitali Arun Tambe, Sin Ying Ma, Michael Timmers, Mary H. Grace, Qing-Li Wu, James E. Simon, George P. McCabe, Mary Ann Lila, Riyi Shi, Jean-Christophe Rochet
Summary: Parkinson's disease (PD) is a neurodegenerative disorder characterized by nigrostriatal degeneration and the spreading of aggregated forms of the presynaptic protein alpha-synuclein (aSyn) throughout the brain. Current treatments for PD only target symptoms, but research shows that isoflavones found in soy products and medicinal plants may have neuroprotective effects that could delay onset and slow progression of PD. Further studies are needed to explore the potential of plant-derived isoflavones as dietary supplements for at-risk individuals and patients with PD.
Article
Chemistry, Multidisciplinary
Priya Prakash, Krupal P. Jethava, Nils Korte, Pablo Izquierdo, Emilia Favuzzi, Indigo V. L. Rose, Kevin A. Guttenplan, Palak Manchanda, Sayan Dutta, Jean-Christophe Rochet, Gord Fishell, Shane A. Liddelow, David Attwell, Gaurav Chopra
Summary: Phagocytosis by glial cells plays a crucial role in regulating brain function, especially in the pathogenesis and progression of Alzheimer's disease. The newly developed Aβ(pH) analogue provides a tool to study the mechanisms of glial cell clearance of Aβ, offering potential insights into Aβ clearance at different stages of AD.