Article
Chemistry, Multidisciplinary
Adriana Di Nanni, Ran Sing Saw, Umberto M. Battisti, Gregory D. Bowden, Adam Boeckermann, Kaare Bjerregaard-Andersen, Bernd J. Pichler, Kristina Herfert, Matthias M. Herth, Andreas Maurer
Summary: This study aimed to develop a selective αSYN PET tracer by designing and screening a library of 2-styrylbenzothiazoles based on the selective fluorescent probe RB1. The lead compounds PFSB and MFSB showed enhanced affinity to αSYN and preserved selectivity over Aβ. In vitro and in vivo experiments demonstrated the successful crossing of the blood-brain barrier and uptake in the brain by [F-18]MFSB.
Article
Chemistry, Analytical
Yinghua Guo, Lei Yin, Xuhong Qian, Youjun Yang, Xiao Luo
Summary: A new principle called PET/d-PET (PdP) pairing is reported for the rational design of two-channel probes. Two fluorophores in a PdP-type probe mutually quench their fluorescence. When an analyte-of-interest is present, the PdP pair converts to a FRET pair for signaling. Rh-TROX, which combines a rhodamine fluorophore with an ROS-sensitive probe (TotalROX), is an embodiment of this principle. The PdP principle offers the possibility to develop probes for a range of substrates.
ANALYTICAL CHEMISTRY
(2023)
Article
Polymer Science
Malgorzata Sypniewska, Anna Kaczmarek-Kedziera, Alexandra Apostoluk, Vitaliy Smokal, Anastasiia Krupka, Robert Szczesny, Beata Derkowska-Zielinska
Summary: The aim of this study was to investigate the influence of various StQ substituents on the luminescence, structural, and optical properties of StQ-containing copolymers. The study found that the change in the nature of the substituent affects the emission band wavelength and can cause a transition in fluorescence color. FTIR and Raman spectroscopies were used to measure the structural properties, while absorbance measurements provided the optical parameters. Computational DFT analysis supported the application of these systems in optoelectronic devices.
Article
Biochemistry & Molecular Biology
Pankaj Gaur, Maksym Galkin, Andrii Kurochka, Subrata Ghosh, Dmytro A. Yushchenko, Volodymyr V. Shvadchak
Summary: In this study, two molecular rotor-based probes RB1 and RB2 are presented, with RB1 showing outstanding absorption red-shift and high fluorescence enhancement, exhibiting high affinity and selective staining ability for alpha-synuclein fibrils in living cells. RB1 can be used for intracellular imaging of alpha-synuclein fibrils due to its strong binding affinity and cell-permeable nature.
ACS CHEMICAL NEUROSCIENCE
(2021)
Review
Chemistry, Medicinal
Spela Korat, Natasha Shalina Rajani Bidesi, Federica Bonanno, Adriana Di Nanni, Anh Nguyen Nhat Hoang, Kristina Herfert, Andreas Maurer, Umberto Maria Battisti, Gregory David Bowden, David Thonon, Danielle Vugts, Albert Dirk Windhorst, Matthias Manfred Herth
Summary: The development of selective alpha-syn PET tracers faces challenges including low alpha-syn abundance, the need for high-affinity ligands, and the co-localization issue with other proteins. This review provides a comprehensive overview of current efforts in the development of selective alpha-syn PET tracers.
Article
Chemistry, Multidisciplinary
Angela Weigert Munoz, Kevin M. Meighen-Berger, Stephan M. Hacker, Matthias J. Feige, Stephan A. Sieber
Summary: This study elucidates the target scope of catechol-containing bioactive molecules from diverse foods and drugs using a mass spectrometry-based competitive chemical proteomics approach. The results reveal that these molecules bind to proteins associated with the endoplasmic reticulum and activate the unfolded protein response, potentially explaining the health-promoting effects of catechol-containing natural products.
Article
Radiology, Nuclear Medicine & Medical Imaging
Laura Kuebler, Sabrina Buss, Andrei Leonov, Sergey Ryazanov, Felix Schmidt, Andreas Maurer, Daniel Weckbecker, Anne M. Landau, Thea P. Lillethorup, Daniel Bleher, Ran Sing Saw, Bernd J. Pichler, Christian Griesinger, Armin Giese, Kristina Herfert
Summary: The newly developed MODAG-001 PET tracer based on anle138b showed high affinity in vitro and good penetration and stability in the mouse brain. However, no detectable binding to aggregated alpha SYN was found in human brain sections of LBD cases, possibly due to low abundance of aggregated alpha SYN against background protein.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2021)
Article
Neurosciences
Sahar Roshanbin, Mengfei Xiong, Greta Hultqvist, Linda Soderberg, Olof Zachrisson, Silvio Meier, Sara Ekmark-Lewen, Joakim Bergstrom, Martin Ingelsson, Dag Sehlin, Stina Syvanen
Summary: By utilizing bispecific antibodies for PET imaging, alpha SYN was successfully visualized in the mouse brain, showing potential application in synucleinopathies. However, challenges remain in imaging intracellular alpha SYN inclusions.
Article
Clinical Neurology
Patrick Oeckl, Marina Bluma, Marco Bucci, Steffen Halbgebauer, Konstantinos Chiotis, Anna Sandebring-Matton, Nicholas J. Ashton, Guglielmo Di Molfetta, Lana Grotschel, Miia Kivipelto, Kaj Blennow, Henrik Zetterberg, Irina Savitcheva, Agneta Nordberg, Markus Otto
Summary: Plasma beta-synuclein levels were found to be higher in individuals with Alzheimer's disease and mild cognitive impairment with amyloid-beta positivity. It demonstrated good discrimination and prediction of amyloid-beta status. The correlation between plasma beta-synuclein and amyloid-beta PET was observed in multiple cortical regions. These findings suggest that beta-synuclein is not a direct marker of amyloid-beta pathology and highlight the different longitudinal dynamics of synaptic degeneration and amyloid deposition in Alzheimer's disease.
ALZHEIMERS & DEMENTIA
(2023)
Article
Multidisciplinary Sciences
Kathryn J. C. Watt, Richard M. Meade, Tony D. James, Jody M. Mason
Summary: Parkinson's disease is the second most common neurodegenerative disease, but there are currently no disease-modifying treatments available. Diagnosis at the earliest stages and monitoring disease progression at a biochemical level are also lacking.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Pengju Nie, Teja Kalidindi, Veronica L. Nagle, Xianzhong Wu, Thomas Li, George P. Liao, Georgia Frost, Kelly E. Henry, Blesida Punzalan, Lukas M. Carter, Jason S. Lewis, Naga Vara Kishore Pillarsetty, Yue-Ming Li
Summary: The study developed a novel PET imaging agent, [I-124]-PN67, based on GSI structure for assessing gamma-secretase activity and target engagement of clinical GSIs. In vitro binding assays demonstrated the probe's high specificity, and PET imaging studies in mouse models showed increased uptake in tumors, indicating gamma-secretase specific tumor accumulation. The results suggest that [I-124]-PN67 could be a valuable tool for evaluating the effectiveness of GSIs in cancer treatment.
CLINICAL CANCER RESEARCH
(2021)
Article
Biotechnology & Applied Microbiology
Edward Chau, Jin Ryoun Kim
Summary: In this study, a new molecular probe, PG65-MIMO, was developed and shown to provide comprehensive information on the aggregation states of alpha-synuclein (alpha S). It fills the technological gap in alpha S detection and offers a promising tool for studying Parkinson's Disease.
BIOCHEMICAL ENGINEERING JOURNAL
(2022)
Article
Neurosciences
Majken B. Thomsen, Sara A. Ferreira, Anna C. Schacht, Jan Jacobsen, Mette Simonsen, Cristine Betzer, Poul H. Jensen, David J. Brooks, Anne M. Landau, Marina Romero-Ramos
Summary: The study demonstrates that intrastriatal injection of a-syn fibrils induces progressive synaptic dysfunction and degeneration of dopamine terminals prior to cell death. PET imaging shows a gradual decrease in VMAT2 and SV2A binding in the ipsilateral striatum, while misfolded a-syn pathology spreads anatomically connected regions and becomes bilateral over time. The presence of MHCII positive ramified microglia indicates neuroinflammation in the injected striatum and substantia nigra.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Engineering, Chemical
Renwen Tian, Yan Sun
Summary: The use of α-synuclein as a fusion chaperone resulted in improved enzymatic performance of PETase, with the fusion enzymes exhibiting higher activity and stability compared to PETase alone. The fusion proteins showed significantly enhanced PET degradation capability, possibly due to the binding affinity of the fused α-synuclein domain for PET.
CHINESE JOURNAL OF CHEMICAL ENGINEERING
(2023)
Article
Behavioral Sciences
Ruiqing Ni
Summary: Animal models of α-synucleinopathies have greatly contributed to the understanding of the disease and the development of therapeutics. Recent advances in positron emission tomography have allowed the noninvasive visualization of molecular alterations and behavioral dysfunctions in these animal models. This review focuses on the development of new PET tracers and studies of α-synuclein and neurotransmitter receptor deficits in Parkinson's disease animal models.
BEHAVIOURAL BRAIN RESEARCH
(2023)