Article
Biochemistry & Molecular Biology
Ana Belen Uceda, Juan Frau, Bartolome Vilanova, Miquel Adrover
Summary: Parkinson's disease is characterized by the degeneration of dopaminergic neurons and the accumulation of Lewy bodies. Previous studies have examined the molecular mechanism linking nitroxidation, aS aggregation, and PD, but the impact of nitroxidation on the physiological function of aS was unclear. Our research found that nitroxidation of Y39 lengthened the disordered stretch between two consecutive alpha-helices and prevented aS from functioning as a catalyst for the clustering and fusion of synaptic vesicles.
Article
Biochemistry & Molecular Biology
Ana Belen Uceda, Juan Frau, Bartolome Vilanova, Miquel Adrover
Summary: Human alpha-synuclein (α S) is an intrinsically disordered protein highly expressed in dopaminergic neurons. Its amyloid aggregates are considered a hallmark of Parkinson's disease (PD). The oxidation of alpha S's methionine residues (MetO) affects its affinity towards anionic micelles and synaptic-like vesicles, impairing its physiological function as a catalyst of vesicle clustering and fusion.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Analytical
Mohamed Sharafeldin, Shijun Yan, Cheng Jiang, George K. Tofaris, Jason J. Davis
Summary: We present a scalable, fast, and low-cost method for extracting cargo proteins from exosome subpopulations using an alternating (AC) magnetic field to facilitate the mixing of antibody-coated magnetic beads (MBs) with serum samples. By applying this method, we were able to achieve high capture efficiencies of >70% from <50 μL of neat serum in just 30 minutes. This approach, when combined with array-based assaying and a standard duplex electrochemical sandwich ELISA, enabled the detection of sub pg/mL levels of α-synuclein content with excellent precision and a sample-to-answer time of approximately 75 minutes. The high performance and semi-automation of this method hold promise for low-cost Parkinson's disease diagnostics and exosomal biomarker analyses.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Christian Hoffmann, Roberto Sansevrino, Giuseppe Morabito, Chinyere Logan, R. Martin Vabulas, Ayse Ulusoy, Marcelo Ganzella, Dragomir Milovanovic
Summary: The regulation of neurotransmission relies on the interaction between synapsin and alpha-synuclein, with the presence of synaptic vesicles enhancing their condensation into functional clusters. The molar ratio between synapsin and alpha-synuclein is crucial for the formation of these clusters and understanding their molecular mechanisms is important for clarifying the pathogenesis of synucleinopathies.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Neurosciences
Yasir Hasan Siddique
Summary: Alpha-synuclein is a protein abundant in the brain, controlling the movement of synaptic vesicles. Overexpression leads to Lewy body formation and damage to dopaminergic neurons, implicated in the progression of Parkinson's Disease. Aggregates of alpha-synuclein exhibit prion-like behavior.
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
(2021)
Article
Biochemistry & Molecular Biology
Meewhi Kim, Ilya Bezprozvanny
Summary: This paper proposes a novel hypothesis that α-synuclein (ASYN) functions as a DA+/H+ exchanger, facilitating dopamine transport across synaptic vesicle (SV) membrane by utilizing the proton gradient between the SV lumen and cytoplasm. The proposed hypothesis suggests that ASYN's normal physiological role is to fine-tune dopamine levels in SVs based on cytosolic dopamine concentration and intraluminal pH. This hypothesis provides new insights into ASYN's biological function and its role in Parkinson's disease (PD) pathogenesis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Cell Biology
Benjamin Feller, Aurelie Fallon, Wen Luo, Phuong Trang Nguyen, Irina Shlaifer, Alfred Kihoon Lee, Nicolas Chofflet, Nayoung Yi, Husam Khaled, Samer Karkout, Steve Bourgault, Thomas M. Durcan, Hideto Takahashi
Summary: This study shows that beta-isoforms of neurexins (beta-NRXs) interact with alpha-syn preformed fibrils (alpha-syn PFFs) to inhibit beta-NRX-mediated presynaptic organization, providing new insights into the molecular mechanism of synaptic pathology induced by alpha-syn PFFs in synucleinopathies such as Parkinson's disease and dementia with Lewy bodies.
Article
Biochemistry & Molecular Biology
Alina A. Sofronova, Denis V. Pozdyshev, Kseniya V. Barinova, Vladimir I. Muronetz, Pavel I. Semenyuk
Summary: The study found that glycation of GAPDH inhibits its interaction with alpha-synuclein and RNA, potentially influencing the interplay between diabetes and neurodegenerative diseases.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Tapojyoti Das, Meraj Ramezani, David Snead, Cristian Follmer, Peter Chung, Ka Yee Lee, David A. A. Holowka, Barbara A. A. Baird, David Eliezer
Summary: Alpha-synuclein plays an important role in regulating synaptic vesicle cycling, exerting both inhibitory and potentiating effects on vesicle release. The binding affinity of alpha-synuclein to isolated vesicles is a key determinant of its ability to potentiate release.
Article
Immunology
Souren Mkrtchian, Anette Ebberyd, Rosanne E. Veerman, Maria Mendez-Lago, Susanne Gabrielsson, Lars I. Eriksson, Marta Gomez-Galan
Summary: Surgical interventions can trigger a cascade of molecular, cellular, and neural signaling responses that affect remote organs, including the brain. In this study, the researchers explored extracellular vesicles (EVs) as potential mediators and found significant differential expression of proteins and miRNAs in circulating EVs after surgery. They suggest that these EVs may modify the extracellular matrix of recipient cells and regulate metabolic processes, potentially mediating the remote effects of surgery on the brain.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Kevin Burbidge, David J. Rademacher, Jessica Mattick, Stephanie Zack, Andrea Grillini, Luc Bousset, Ochan Kwon, Konrad Kubicki, Alexander Simon, Ronald Melki, Edward M. Campbell
Summary: Numerous lines of evidence support the notion that misfolding and accumulation of SNCA/alpha-synuclein leads to neuronal pathology in Parkinson's disease and other synucleinopathies. The cell-to-cell transfer of misfolded SNCA is believed to contribute to disease progression and spread of pathology in the brain. Studies suggest that both pathological and non-pathological forms of SNCA are secreted through an autophagy-dependent unconventional secretion pathway.
Article
Clinical Neurology
Shay Herman, Ruth Djaldetti, Brit Mollenhauer, Daniel Offen
Summary: This study found that extracellular vesicles derived from the cerebrospinal fluid of Parkinson's disease patients can propagate alpha-synuclein aggregation in healthy mice and induce Parkinson's disease-like symptoms and pathology, including hyposmia, motor behavior impairments, dopaminergic neurodegeneration, and neuroinflammation.
Article
Clinical Neurology
Shay Herman, Ruth Djaldetti, Brit Mollenhauer, Daniel Offen
Summary: Parkinson's disease is characterized by the accumulation of misfolded α-synuclein protein, leading to neuronal death. Recent studies suggest that misfolded α-synuclein can spread in a prion-like manner and induce pathological aggregates in healthy neurons. Extracellular vesicles derived from the CSF of Parkinson's disease patients can propagate α-synuclein aggregation and trigger disease-like symptoms.
Article
Biochemistry & Molecular Biology
Chen-Chih Chung, Lung Chan, Jia-Hung Chen, Yi-Chieh Hung, Chien-Tai Hong
Summary: Plasma extracellular vesicle (EV) alpha-synuclein levels were significantly lower in patients with Parkinson's disease (PD) compared to controls, and were associated with the severity of akinetic-rigidity symptoms in PD patients. This study supports the diagnostic potential and clinical relevance of plasma EV alpha-synuclein as a biomarker for PD subtyping.
Review
Clinical Neurology
Paolo Calabresi, Giulia Di Lazzaro, Gioia Marino, Federica Campanelli, Veronica Ghiglieri
Summary: The critical role of alpha-synuclein in Parkinson's disease has been discovered, but current treatments still face challenges. Developing cellular and animal models helps understand the physiological and pathological functions of alpha-synuclein, as well as the pathogenesis of Parkinson's disease.
Article
Chemistry, Physical
Rafael Ramis, Rodrigo Casasnovas, Laura Marino, Juan Frau, Miguel Adrover, Bartolome Vilanova, Nelaine Mora-Diez, Joaquin Ortega-Castro
INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Humberto Martinez-Orozco, Laura Marino, Ana Belen Uceda, Joaquin Ortega-Castro, Bartolome Vilanova, Juan Frau, Miquel Adrover
ACS CHEMICAL NEUROSCIENCE
(2019)
Article
Chemistry, Inorganic & Nuclear
Ana B. Uceda, Laura Marino, Miguel Adrover, Bartolome Vilanova
INORGANICA CHIMICA ACTA
(2020)
Article
Environmental Sciences
Miquel Oliver, Miquel Adrover, Antonio Frontera, Joaquin Ortega-Castro, Manuel Miro
SCIENCE OF THE TOTAL ENVIRONMENT
(2020)
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
Biochemistry & Molecular Biology
Ana Belen Uceda, Josefa Donoso, Juan Frau, Bartolome Vilanova, Miquel Adrover
Summary: Frataxin is a mitochondrial protein crucial for regulating oxidative stress balance and protecting neurons. Research has shown that both human and yeast frataxins can inhibit the formation of reactive oxygen species and protect oxidation-prone proteins. This suggests that frataxins act as a shield against oxidation and could potentially be used to prevent neurological disorders associated with oxidative stress.
Article
Biochemistry & Molecular Biology
Ana Belen Uceda, Juan Frau, Bartolome Vilanova, Miquel Adrover
Summary: Human alpha-synuclein (α S) is an intrinsically disordered protein highly expressed in dopaminergic neurons. Its amyloid aggregates are considered a hallmark of Parkinson's disease (PD). The oxidation of alpha S's methionine residues (MetO) affects its affinity towards anionic micelles and synaptic-like vesicles, impairing its physiological function as a catalyst of vesicle clustering and fusion.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Plant Sciences
Ivan Cortes-Fernandez, Antoni Sureda, Miquel Adrover, Giovanni Caprioli, Filippo Maggi, Lorenzo Gil-Vives, Xavier Capo
Summary: The study investigated the effects of E. maritimum rhizome extract on the antioxidant and inflammatory response in human immune cells. The extract showed a high diversity of pharmacologically bioactive compounds and exerted antioxidant and anti-inflammatory effects on Jurkat cells by inducing an antioxidant response, reducing cytokine and nitric oxide release, and inhibiting the expression of pro-inflammatory genes.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Rafael Ramis, Joaquin Ortega-Castro, Bartolome Vilanova, Miquel Adrover, Juan Frau
Article
Chemistry, Multidisciplinary
Laura Marino, Rafael Ramis, Rodrigo Casasnovas, Joaquin Ortega-Castro, Bartolome Vilanova, Juan Frau, Miquel Adrover