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Effect of Familial Parkinson's Disease Point Mutations A30P and A53T on the Structural Properties, Aggregation, and Fibrillation of Human α-Synuclein†

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Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, and Institute for Biological Instrumentation, Russian Academy of Sciences, 142292 Pushchino, Moscow Region, Russia
Cite this: Biochemistry 2001, 40, 38, 11604–11613
Publication Date (Web):August 28, 2001
https://doi.org/10.1021/bi010616g
Copyright © 2001 American Chemical Society
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    Abstract

    Parkinson's disease involves the loss of dopaminergic neurons in the substantia nigra, leading to movement disorders. The pathological hallmark of Parkinson's disease is the presence of Lewy bodies and Lewy neurites, which are intracellular inclusions consisting primarily of α-synuclein. Although essentially all cases of sporadic and early-onset Parkinson's disease are of unknown etiology, two point mutations (A53T and A30P) in the α-synuclein gene have been identified in familial early-onset Parkinson's disease. Previous reports have shown that mutant α-synuclein may form fibrils more rapidly than wild-type protein. To determine the underlying molecular basis for the enhanced fibrillation of the mutants, the structural properties, responses to changes in the environment, and propensity to aggregate of wild-type, A30P, and A53T α-synucleins were systematically investigated. A variety of biophysical methods, including far-UV circular dichroism, FTIR, small-angle X-ray scattering, and light scattering, were employed. Neither the natively unfolded nor the partially folded intermediate conformations are affected by the familial Parkinson's disease point mutations. However, both mutants underwent self-association more readily than the wild type (i.e., at much lower protein concentration and more rapidly). We attribute this effect to the increased propensity of their partially folded intermediates to aggregate, rather than to any changes in the monomeric natively unfolded species. This increased propensity of these mutants to aggregate, relative to wild-type α-synuclein, would account for the correlation of these mutations with Parkinson's disease.

    †

     This research was supported by a grant from the National Institutes of Health. V.N.U. was supported by fellowships from the Parkinson's Institute and the National Parkinson's Foundation.

    ‡

     These authors made equal contributions.

    §

     University of California, Santa Cruz.

    *

     To whom correspondence should be addressed. Fax:  +1-831-459-2935. E-mail:  [email protected].

    ‖

     Russian Academy of Sciences.

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    8. Veronika Sachsenhauser, Xiexiong Deng, Hyun-hee Kim, Maja Jankovic, James C.A. Bardwell. Yeast Tripartite Biosensors Sensitive to Protein Stability and Aggregation Propensity. ACS Chemical Biology 2020, 15 (4) , 1078-1088. https://doi.org/10.1021/acschembio.0c00083
    9. José Gallardo, Carmen Escalona-Noguero, Begoña Sot. Role of α-Synuclein Regions in Nucleation and Elongation of Amyloid Fiber Assembly. ACS Chemical Neuroscience 2020, 11 (6) , 872-879. https://doi.org/10.1021/acschemneuro.9b00527
    10. Viktoria C. Ruf, Georg S. Nübling, Sophia Willikens, Song Shi, Felix Schmidt, Johannes Levin, Kai Bötzel, Frits Kamp, Armin Giese. Different Effects of α-Synuclein Mutants on Lipid Binding and Aggregation Detected by Single Molecule Fluorescence Spectroscopy and ThT Fluorescence-Based Measurements. ACS Chemical Neuroscience 2019, 10 (3) , 1649-1659. https://doi.org/10.1021/acschemneuro.8b00579
    11. Guanglin Kuang, N. Arul Murugan, Hans Ågren. Mechanistic Insight into the Binding Profile of DCVJ and α-Synuclein Fibril Revealed by Multiscale Simulations. ACS Chemical Neuroscience 2019, 10 (1) , 610-617. https://doi.org/10.1021/acschemneuro.8b00465
    12. Marija Iljina, Alexander J. Dear, Gonzalo A. Garcia, Suman De, Laura Tosatto, Patrick Flagmeier, Daniel R. Whiten, Thomas C. T. Michaels, Daan Frenkel, Christopher M. Dobson, Tuomas P. J. Knowles, David Klenerman. Quantifying Co-Oligomer Formation by α-Synuclein. ACS Nano 2018, 12 (11) , 10855-10866. https://doi.org/10.1021/acsnano.8b03575
    13. Cagla Sahin, Lars Kjær, Mette Solvang Christensen, Jannik N. Pedersen, Gunna Christiansen, Adriana-Michelle Wolf Pérez, Ian Max Møller, Jan J. Enghild, Jan S. Pedersen, Knud Larsen, Daniel E. Otzen. α-Synucleins from Animal Species Show Low Fibrillation Propensities and Weak Oligomer Membrane Disruption. Biochemistry 2018, 57 (34) , 5145-5158. https://doi.org/10.1021/acs.biochem.8b00627
    14. Sanjay Kumar, Deepak Kumar Jangir, Roshan Kumar, Manisha Kumari, Neel Sarovar Bhavesh, and Tushar Kanti Maiti . Role of Sporadic Parkinson Disease Associated Mutations A18T and A29S in Enhanced α-Synuclein Fibrillation and Cytotoxicity. ACS Chemical Neuroscience 2018, 9 (2) , 230-240. https://doi.org/10.1021/acschemneuro.6b00430
    15. Narendra Nath Jha, Srivastav Ranganathan, Rakesh Kumar, Surabhi Mehra, Rajlaxmi Panigrahi, Ambuja Navalkar, Dhiman Ghosh, Ashutosh Kumar, Ranjith Padinhateeri, and Samir K. Maji . Complexation of NAC-Derived Peptide Ligands with the C-Terminus of α-Synuclein Accelerates Its Aggregation. Biochemistry 2018, 57 (5) , 791-804. https://doi.org/10.1021/acs.biochem.7b01090
    16. Liang Xu, Buyong Ma, Ruth Nussinov, and Damien Thompson . Familial Mutations May Switch Conformational Preferences in α-Synuclein Fibrils. ACS Chemical Neuroscience 2017, 8 (4) , 837-849. https://doi.org/10.1021/acschemneuro.6b00406
    17. Arshdeep Sidhu, Ine Segers-Nolten, Vincent Raussens, Mireille M. A. E. Claessens, and Vinod Subramaniam . Distinct Mechanisms Determine α-Synuclein Fibril Morphology during Growth and Maturation. ACS Chemical Neuroscience 2017, 8 (3) , 538-547. https://doi.org/10.1021/acschemneuro.6b00287
    18. Jessica L. Billings, Dominic J. Hare, Milawaty Nurjono, Irene Volitakis, Robert A. Cherny, Ashley I. Bush, Paul A. Adlard, and David I. Finkelstein . Effects of Neonatal Iron Feeding and Chronic Clioquinol Administration on the Parkinsonian Human A53T Transgenic Mouse. ACS Chemical Neuroscience 2016, 7 (3) , 360-366. https://doi.org/10.1021/acschemneuro.5b00305
    19. Srabasti Acharya, Shreya Saha, Basir Ahmad, and Lisa J. Lapidus . Effects of Mutations on the Reconfiguration Rate of α-Synuclein. The Journal of Physical Chemistry B 2015, 119 (50) , 15443-15450. https://doi.org/10.1021/acs.jpcb.5b10136
    20. Joe Kakish, Dongsoo Lee, and Jeremy S. Lee . Drugs That Bind to α-Synuclein: Neuroprotective or Neurotoxic?. ACS Chemical Neuroscience 2015, 6 (12) , 1930-1940. https://doi.org/10.1021/acschemneuro.5b00172
    21. Joe Kakish, Omid Tavassoly, and Jeremy S. Lee . Rasagiline, a Suicide Inhibitor of Monoamine Oxidases, Binds Reversibly to α-Synuclein. ACS Chemical Neuroscience 2015, 6 (2) , 347-355. https://doi.org/10.1021/cn5002914
    22. Laurie Bédard, Thierry Lefèvre, Émilie Morin-Michaud, and Michèle Auger . Besides Fibrillization: Putative Role of the Peptide Fragment 71–82 on the Structural and Assembly Behavior of α-Synuclein. Biochemistry 2014, 53 (41) , 6463-6472. https://doi.org/10.1021/bi5008707
    23. Johnny Habchi, Peter Tompa, Sonia Longhi, and Vladimir N. Uversky . Introducing Protein Intrinsic Disorder. Chemical Reviews 2014, 114 (13) , 6561-6588. https://doi.org/10.1021/cr400514h
    24. Francois-Xavier Theillet, Andres Binolfi, Tamara Frembgen-Kesner, Karan Hingorani, Mohona Sarkar, Ciara Kyne, Conggang Li, Peter B. Crowley, Lila Gierasch, Gary J. Pielak, Adrian H. Elcock, Anne Gershenson, and Philipp Selenko . Physicochemical Properties of Cells and Their Effects on Intrinsically Disordered Proteins (IDPs). Chemical Reviews 2014, 114 (13) , 6661-6714. https://doi.org/10.1021/cr400695p
    25. Alexey V. Krasnoslobodtsev, Ivan L. Volkov, Josephat M. Asiago, Jagadish Hindupur, Jean-Christophe Rochet, and Yuri L. Lyubchenko . α-Synuclein Misfolding Assessed with Single Molecule AFM Force Spectroscopy: Effect of Pathogenic Mutations. Biochemistry 2013, 52 (42) , 7377-7386. https://doi.org/10.1021/bi401037z
    26. Domenica Dibenedetto, Giulia Rossetti, Rocco Caliandro, and Paolo Carloni . A Molecular Dynamics Simulation-Based Interpretation of Nuclear Magnetic Resonance Multidimensional Heteronuclear Spectra of α-Synuclein·Dopamine Adducts. Biochemistry 2013, 52 (38) , 6672-6683. https://doi.org/10.1021/bi400367r
    27. Hai-Yan Wang, Zhen Gu, Chan Cao, Jian Wang, and Yi-Tao Long . Analysis of a Single α-Synuclein Fibrillation by the Interaction with a Protein Nanopore. Analytical Chemistry 2013, 85 (17) , 8254-8261. https://doi.org/10.1021/ac401496x
    28. Orkid Coskuner and Olivia Wise-Scira . Structures and Free Energy Landscapes of the A53T Mutant-Type α-Synuclein Protein and Impact of A53T Mutation on the Structures of the Wild-Type α-Synuclein Protein with Dynamics. ACS Chemical Neuroscience 2013, 4 (7) , 1101-1113. https://doi.org/10.1021/cn400041j
    29. Michael Rabe, Alice Soragni, Nicholas P. Reynolds, Dorinel Verdes, Ennio Liverani, Roland Riek, and Stefan Seeger . On-Surface Aggregation of α-Synuclein at Nanomolar Concentrations Results in Two Distinct Growth Mechanisms. ACS Chemical Neuroscience 2013, 4 (3) , 408-417. https://doi.org/10.1021/cn3001312
    30. Olivia Wise-Scira, Ahmet Kemal Aloglu, Aquila Dunn, Isin Tuna Sakallioglu, and Orkid Coskuner . Structures and Free Energy Landscapes of the Wild-Type and A30P Mutant-Type α-Synuclein Proteins with Dynamics. ACS Chemical Neuroscience 2013, 4 (3) , 486-497. https://doi.org/10.1021/cn300198q
    31. Olivia Wise-Scira, Aquila Dunn, Ahmet K. Aloglu, Isin T. Sakallioglu, and Orkid Coskuner . Structures of the E46K Mutant-Type α-Synuclein Protein and Impact of E46K Mutation on the Structures of the Wild-Type α-Synuclein Protein. ACS Chemical Neuroscience 2013, 4 (3) , 498-508. https://doi.org/10.1021/cn3002027
    32. Jacob A. Irwin, H. Edward Wong, and Inchan Kwon . Different Fates of Alzheimer’s Disease Amyloid-β Fibrils Remodeled by Biocompatible Small Molecules. Biomacromolecules 2013, 14 (1) , 264-274. https://doi.org/10.1021/bm3016994
    33. Nathan P. Cook, Kiri Kilpatrick, Laura Segatori, and Angel A. Martí . Detection of α-Synuclein Amyloidogenic Aggregates in Vitro and in Cells using Light-Switching Dipyridophenazine Ruthenium(II) Complexes. Journal of the American Chemical Society 2012, 134 (51) , 20776-20782. https://doi.org/10.1021/ja3100287
    34. Orly Ullman, Charles K. Fisher, and Collin M. Stultz . Explaining the Structural Plasticity of α-Synuclein. Journal of the American Chemical Society 2011, 133 (48) , 19536-19546. https://doi.org/10.1021/ja208657z
    35. Lijuan Kang, Kuen-Phon Wu, Michele Vendruscolo, and Jean Baum . The A53T Mutation is Key in Defining the Differences in the Aggregation Kinetics of Human and Mouse α-Synuclein. Journal of the American Chemical Society 2011, 133 (34) , 13465-13470. https://doi.org/10.1021/ja203979j
    36. Anjan P. Pandey, Farzin Haque, Jean-Christophe Rochet, and Jennifer S. Hovis . α-Synuclein-Induced Tubule Formation in Lipid Bilayers. The Journal of Physical Chemistry B 2011, 115 (19) , 5886-5893. https://doi.org/10.1021/jp1121917
    37. Jessika Meuvis, Melanie Gerard, Linda Desender, Veerle Baekelandt, and Yves Engelborghs . The Conformation and the Aggregation Kinetics of α-Synuclein Depend on the Proline Residues in Its C-Terminal Region. Biochemistry 2010, 49 (43) , 9345-9352. https://doi.org/10.1021/bi1010927
    38. Kyla Pennington, Jianhe Peng, Chao-Chun Hung, Rosamonde E. Banks and Philip A. Robinson . Differential Effects of Wild-Type and A53T Mutant Isoform of Alpha-Synuclein on the Mitochondrial Proteome of Differentiated SH-SY5Y Cells. Journal of Proteome Research 2010, 9 (5) , 2390-2401. https://doi.org/10.1021/pr901102d
    39. Christina R. Bodner, Alexander S. Maltsev, Christopher M. Dobson and Ad Bax . Differential Phospholipid Binding of α-Synuclein Variants Implicated in Parkinson’s Disease Revealed by Solution NMR Spectroscopy. Biochemistry 2010, 49 (5) , 862-871. https://doi.org/10.1021/bi901723p
    40. Elisa A. Waxman, Joseph R. Mazzulli and Benoit I. Giasson. Characterization of Hydrophobic Residue Requirements for α-Synuclein Fibrillization. Biochemistry 2009, 48 (40) , 9427-9436. https://doi.org/10.1021/bi900539p
    41. M. Soledad Celej, Wouter Caarls, Alexander P. Demchenko and Thomas M. Jovin . A Triple-Emission Fluorescent Probe Reveals Distinctive Amyloid Fibrillar Polymorphism of Wild-Type α-Synuclein and Its Familial Parkinson’s Disease Mutants. Biochemistry 2009, 48 (31) , 7465-7472. https://doi.org/10.1021/bi9003843
    42. Lian Hong and John D. Simon. Binding of Cu(II) to Human α-Synucleins: Comparison of Wild Type and the Point Mutations Associated with the Familial Parkinson’s Disease. The Journal of Physical Chemistry B 2009, 113 (28) , 9551-9561. https://doi.org/10.1021/jp809773y
    43. Megan Grabenauer, Summer L. Bernstein, Jennifer C. Lee, Thomas Wyttenbach, Nicholas F. Dupuis, Harry B. Gray, Jay R. Winkler and Michael T. Bowers. Spermine Binding to Parkinson’s Protein α-Synuclein and Its Disease-Related A30P and A53T Mutants. The Journal of Physical Chemistry B 2008, 112 (35) , 11147-11154. https://doi.org/10.1021/jp801175w
    44. Elemér Vass,, Miklós Hollósi,, Françoise Besson, and, René Buchet. Vibrational Spectroscopic Detection of Beta- and Gamma-Turns in Synthetic and Natural Peptides and Proteins. Chemical Reviews 2003, 103 (5) , 1917-1954. https://doi.org/10.1021/cr000100n
    45. Takashi Ohgita, Hiroki Kono, Izumi Morita, Hiroyuki Oyama, Toshinori Shimanouchi, Norihiro Kobayashi, Hiroyuki Saito. Intramolecular interaction kinetically regulates fibril formation by human and mouse α-synuclein. Scientific Reports 2023, 13 (1) https://doi.org/10.1038/s41598-023-38070-4
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    48. Gurdeep Kaur, Iqubal Singh, Runjhun Tandon, Nitin Tandon. Recent Advancements in Coumarin Based Colorimetric and Fluorescent Chemosensors. Inorganic Chemistry Communications 2023, 466 , 111480. https://doi.org/10.1016/j.inoche.2023.111480
    49. Luisa Maria Gatzemeier, Franc Meyer, Ulf Diederichsen, Tiago Fleming Outeiro. Chemical Synthesis of Alpha‐Synuclein Proteins via Solid‐Phase Peptide Synthesis and Native Chemical Ligation. Chemistry – A European Journal 2023, 29 (33) https://doi.org/10.1002/chem.202300649
    50. Siddhant Sethi, Yasuharu Takashima, Shigetaka Nakamura, Licheng Wan, Nozomi Honda, Kenzo Fujimoto. Acceleration of the Deamination of Cytosine through Photo-Crosslinking. Current Issues in Molecular Biology 2023, 45 (6) , 4687-4700. https://doi.org/10.3390/cimb45060298
    51. Gabriel F. Martins, N. Galamba. Protein aggregation-inhibition: a therapeutic route from Parkinson’s disease to sickle cell anemia. Critical Reviews in Biochemistry and Molecular Biology 2023, 466 , 1-31. https://doi.org/10.1080/10409238.2023.2201406
    52. Peter Riederer, Toshiharu Nagatsu, Moussa B. H. Youdim, Max Wulf, Johannes M. Dijkstra, Jeswinder Sian-Huelsmann. Lewy bodies, iron, inflammation and neuromelanin: pathological aspects underlying Parkinson’s disease. Journal of Neural Transmission 2023, 130 (5) , 627-646. https://doi.org/10.1007/s00702-023-02630-9
    53. Carmen Nanclares, Jonah Poynter, Hector A. Martell-Martinez, Scott Vermilyea, Alfonso Araque, Paulo Kofuji, Michael K. Lee, Ana Covelo. Dysregulation of astrocytic Ca2+ signaling and gliotransmitter release in mouse models of α-synucleinopathies. Acta Neuropathologica 2023, 145 (5) , 597-610. https://doi.org/10.1007/s00401-023-02547-3
    54. Bingkuan Xu, Fengshuo Fan, Yunpeng Liu, Yinghui Liu, Lin Zhou, Haijia Yu. Distinct Effects of Familial Parkinson’s Disease-Associated Mutations on α-Synuclein Phase Separation and Amyloid Aggregation. Biomolecules 2023, 13 (5) , 726. https://doi.org/10.3390/biom13050726
    55. Jaquelini B. Canever, Ericks Sousa Soares, Núbia C.P. de Avelar, Helena I. Cimarosti. Targeting α-synuclein post-translational modifications in Parkinson’s disease. Behavioural Brain Research 2023, 439 , 114204. https://doi.org/10.1016/j.bbr.2022.114204
    56. Phoebe S. Tsoi, My Diem Quan, Josephine C. Ferreon, Allan Chris M. Ferreon. Aggregation of Disordered Proteins Associated with Neurodegeneration. International Journal of Molecular Sciences 2023, 24 (4) , 3380. https://doi.org/10.3390/ijms24043380
    57. Semanti Mukherjee, Arunima Sakunthala, Laxmikant Gadhe, Manisha Poudyal, Ajay Singh Sawner, Pradeep Kadu, Samir K. Maji. Liquid-liquid Phase Separation of α-Synuclein: A New Mechanistic Insight for α-Synuclein Aggregation Associated with Parkinson's Disease Pathogenesis. Journal of Molecular Biology 2023, 435 (1) , 167713. https://doi.org/10.1016/j.jmb.2022.167713
    58. Jessica Dröden, Malte Drescher. Rapid Scan Electron Paramagnetic Resonance Spectroscopy Is a Suitable Tool to Study Intermolecular Interactions of Intrinsically Disordered Protein. Biology 2023, 12 (1) , 79. https://doi.org/10.3390/biology12010079
    59. Takashi Ohgita, Norihiro Namba, Hiroki Kono, Toshinori Shimanouchi, Hiroyuki Saito. Mechanisms of enhanced aggregation and fibril formation of Parkinson’s disease-related variants of α-synuclein. Scientific Reports 2022, 12 (1) https://doi.org/10.1038/s41598-022-10789-6
    60. Rina Nakamura, Toshifumi Akizawa, Motomi Konishi. Structure–Activity Relationship of 5-mer Catalytides, GSGYR and RYGSG. Biomolecules 2022, 12 (12) , 1766. https://doi.org/10.3390/biom12121766
    61. Samantha X. Pancoe, Yanxin J. Wang, Marie Shimogawa, Ryann M. Perez, Sam Giannakoulias, E. James Petersson. Effects of Mutations and Post-Translational Modifications on α-Synuclein In Vitro Aggregation. Journal of Molecular Biology 2022, 434 (23) , 167859. https://doi.org/10.1016/j.jmb.2022.167859
    62. Kathryn J.C. Watt, Richard M. Meade, Robert J. Williams, Jody M. Mason. Anionic lipid vesicles have differential effects on the aggregation of early onset-associated α-synuclein missense mutants. Journal of Biological Chemistry 2022, 298 (12) , 102565. https://doi.org/10.1016/j.jbc.2022.102565
    63. Mitra Pirhaghi, Signe Andrea Frank, Parvez Alam, Janni Nielsen, Vita Sereikaite, Arpit Gupta, Kristian Strømgaard, Maria Andreasen, Deepak Sharma, Ali Akbar Saboury, Daniel Erik Otzen. A penetratin-derived peptide reduces the membrane permeabilization and cell toxicity of α-synuclein oligomers. Journal of Biological Chemistry 2022, 298 (12) , 102688. https://doi.org/10.1016/j.jbc.2022.102688
    64. Gyeongji Yoo, Hyeong Jeon An, Sanghun Yeou, Nam Ki Lee. α-Synuclein Disrupts Vesicle Fusion by Two Mutant-Specific Mechanisms. Molecules and Cells 2022, 45 (11) , 806-819. https://doi.org/10.14348/molcells.2022.0102
    65. Francois-Xavier Theillet, Enrico Luchinat. In-cell NMR: Why and how?. Progress in Nuclear Magnetic Resonance Spectroscopy 2022, 132-133 , 1-112. https://doi.org/10.1016/j.pnmrs.2022.04.002
    66. Arina Yazawa, Kenneth Hensley, Toshio Ohshima. Effects of Lanthionine Ketimine-5-Ethyl Ester on the α-Synucleinopathy Mouse Model. Neurochemical Research 2022, 47 (8) , 2373-2382. https://doi.org/10.1007/s11064-022-03626-9
    67. Chandrakanta Potdar, Alka Kaushal, Aishwarya Raj, Rathijit Mallick, Indrani Datta. Reduction of phosphorylated α-synuclein through downregulation of casein kinase 2α alleviates dopaminergic-neuronal function. Biochemical and Biophysical Research Communications 2022, 615 , 43-48. https://doi.org/10.1016/j.bbrc.2022.05.023
    68. Yuxi Lin, Dai Ito, Je Min Yoo, Mi Hee Lim, Wookyung Yu, Yasushi Kawata, Young-Ho Lee. Dual Effects of Presynaptic Membrane Mimetics on α-Synuclein Amyloid Aggregation. Frontiers in Cell and Developmental Biology 2022, 10 https://doi.org/10.3389/fcell.2022.707417
    69. Shogo Moriya, Michiko Hanazono, Takeshi Fukuhara, Katsuro Iwase, Nobutaka Hattori, Masaki Takiguchi. A53T mutant α-synuclein fibrils formed in macrophage are spread to neurons. Cellular and Molecular Life Sciences 2022, 79 (5) https://doi.org/10.1007/s00018-022-04263-9
    70. Francesca De Giorgi, Vladimir N. Uversky, François Ichas. α-Synuclein Fibrils as Penrose Machines: A Chameleon in the Gear. Biomolecules 2022, 12 (4) , 494. https://doi.org/10.3390/biom12040494
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    75. Laxmikant Gadhe, Arunima Sakunthala, Semanti Mukherjee, Nitisha Gahlot, Riya Bera, Ajay Singh Sawner, Pradeep Kadu, Samir K. Maji. Intermediates of α-synuclein aggregation: Implications in Parkinson's disease pathogenesis. Biophysical Chemistry 2022, 281 , 106736. https://doi.org/10.1016/j.bpc.2021.106736
    76. Anne Christmann, Manuela Gries, Patrik Scholz, Pascal L. Stahr, Jessica Ka Yan Law, Steven Schulte, Monika Martin, Rainer Lilischkis, Sven Ingebrandt, Cornelia M. Keck, Karl-Herbert Schäfer. The antioxidant Rutin counteracts the pathological impact of α -synuclein on the enteric nervous system in vitro. Biological Chemistry 2022, 403 (1) , 103-122. https://doi.org/10.1515/hsz-2021-0259
    77. Ilia M. Golomidov, Evgenia M. Latypova, Elena V. Ryabova, Olga I. Bolshakova, Artem E. Komissarov, Svetlana V. Sarantseva. Reduction of the α-synuclein expression promotes slowing down early neuropathology development in the Drosophila model of Parkinson’s disease. Journal of Neurogenetics 2022, 36 (1) , 1-10. https://doi.org/10.1080/01677063.2022.2064462
    78. Md Ezazul Haque, Mahbuba Akther, Shofiul Azam, In‐Su Kim, Yuxi Lin, Young‐Ho Lee, Dong‐Kug Choi. Targeting α‐synuclein aggregation and its role in mitochondrial dysfunction in Parkinson's disease. British Journal of Pharmacology 2022, 179 (1) , 23-45. https://doi.org/10.1111/bph.15684
    79. Di Liu, Jian-Jun Guo, Ji-Hui Su, Alexander Svanbergsson, Lin Yuan, Caroline Haikal, Wen Li, Gunnar Gouras, Jia-Yi Li. Differential seeding and propagating efficiency of α-synuclein strains generated in different conditions. Translational Neurodegeneration 2021, 10 (1) https://doi.org/10.1186/s40035-021-00242-5
    80. André D. G. Leitão, Paulina Rudolffi-Soto, Alexandre Chappard, Akshay Bhumkar, Derrick Lau, Dominic J. B. Hunter, Yann Gambin, Emma Sierecki. Selectivity of Lewy body protein interactions along the aggregation pathway of α-synuclein. Communications Biology 2021, 4 (1) https://doi.org/10.1038/s42003-021-02624-x
    81. Aurélie 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. Neuroprotective mechanisms of red clover and soy isoflavones in Parkinson's disease models. Food & Function 2021, 12 (23) , 11987-12007. https://doi.org/10.1039/D1FO00007A
    82. Di Hu, Zunren Liu, Xin Qi. Mitochondrial Quality Control Strategies: Potential Therapeutic Targets for Neurodegenerative Diseases?. Frontiers in Neuroscience 2021, 15 https://doi.org/10.3389/fnins.2021.746873
    83. Parveen Salahuddin, Munazza Tamkeen Fatima, Vladimir N. Uversky, Rizwan Hasan Khan, Zeyaul Islam, Mohammad Furkan. The role of amyloids in Alzheimer's and Parkinson's diseases. International Journal of Biological Macromolecules 2021, 190 , 44-55. https://doi.org/10.1016/j.ijbiomac.2021.08.197
    84. Sheila K. Pirooznia, Liana S. Rosenthal, Valina L. Dawson, Ted M. Dawson, . Parkinson Disease: Translating Insights from Molecular Mechanisms to Neuroprotection. Pharmacological Reviews 2021, 73 (4) , 1204-1268. https://doi.org/10.1124/pharmrev.120.000189
    85. Fide Sevgi, Eva M. Brauchle, Daniel A. Carvajal Berrio, Katja Schenke-Layland, Nicolas Casadei, Madhuri S. Salker, Olaf Riess, Yogesh Singh. Imaging of α-Synuclein Aggregates in a Rat Model of Parkinson’s Disease Using Raman Microspectroscopy. Frontiers in Cell and Developmental Biology 2021, 9 https://doi.org/10.3389/fcell.2021.664365
    86. Dongjian Zhu, Shilei Jiang, Wei Zhao, Xiaowei Yan, Wei Xie, Yuhao Xiong, Sujuan Wang, Wen Cai, Youjun Gao, Aishan Ren. A novel ratiometric fluorescent probe for sensitive and selective detection of Cu2+ based on Boranil derivatives. Inorganica Chimica Acta 2021, 524 , 120438. https://doi.org/10.1016/j.ica.2021.120438
    87. Sen Xu, Lei Zhang, Yameng Zhao, Yongquan Luo, Bohao Yu, Weibing Zhang. A magnetic functionalized lanthanide fluorescent sensor for detection of trace zinc ion. Research on Chemical Intermediates 2021, 47 (8) , 3487-3500. https://doi.org/10.1007/s11164-021-04472-0
    88. Rossana Di Martino, Maria Sisalli, Rossana Sirabella, Salvatore Della Notte, Domenica Borzacchiello, Antonio Feliciello, Lucio Annunziato, Antonella Scorziello. Ncx3-Induced Mitochondrial Dysfunction in Midbrain Leads to Neuroinflammation in Striatum of A53t-α-Synuclein Transgenic Old Mice. International Journal of Molecular Sciences 2021, 22 (15) , 8177. https://doi.org/10.3390/ijms22158177
    89. Cameron Wells, Samuel Brennan, Matt Keon, Lezanne Ooi. The role of amyloid oligomers in neurodegenerative pathologies. International Journal of Biological Macromolecules 2021, 181 , 582-604. https://doi.org/10.1016/j.ijbiomac.2021.03.113
    90. Pierpaolo Risiglione, Federica Zinghirino, Maria Carmela Di Rosa, Andrea Magrì, Angela Messina. Alpha-Synuclein and Mitochondrial Dysfunction in Parkinson’s Disease: The Emerging Role of VDAC. Biomolecules 2021, 11 (5) , 718. https://doi.org/10.3390/biom11050718
    91. Michele Perni, Annemieke van der Goot, Ryan Limbocker, Tjakko J. van Ham, Francesco A. Aprile, Catherine K. Xu, Patrick Flagmeier, Karen Thijssen, Pietro Sormanni, Giuliana Fusco, Serene W. Chen, Pavan K. Challa, Julius B. Kirkegaard, Romain F. Laine, Kai Yu Ma, Martin B. D. Müller, Tessa Sinnige, Janet R. Kumita, Samuel I. A. Cohen, Renée Seinstra, Gabriele S. Kaminski Schierle, Clemens F. Kaminski, Denise Barbut, Alfonso De Simone, Tuomas P. J. Knowles, Michael Zasloff, Ellen A. A. Nollen, Michele Vendruscolo, Christopher M. Dobson. Comparative Studies in the A30P and A53T α-Synuclein C. elegans Strains to Investigate the Molecular Origins of Parkinson's Disease. Frontiers in Cell and Developmental Biology 2021, 9 https://doi.org/10.3389/fcell.2021.552549
    92. Qihua You, Yihua Zhuo, Yadong Feng, Yujuan Xiao, Yanyu Zhang, Lei Zhang. A highly selective fluorescent probe for the sensing of Cu 2+ based on the hydrolysis of a quinoline-2-carboxylate and its application in cell imaging. Journal of Chemical Research 2021, 45 (3-4) , 315-321. https://doi.org/10.1177/1747519820973929
    93. Magdalena I. Ivanova, Yuxi Lin, Young-Ho Lee, Jie Zheng, Ayyalusamy Ramamoorthy. Biophysical processes underlying cross-seeding in amyloid aggregation and implications in amyloid pathology. Biophysical Chemistry 2021, 269 , 106507. https://doi.org/10.1016/j.bpc.2020.106507
    94. James M. Gruschus. Attack of the Oligomers – Alpha-synuclein amyloid oligomers and their pathogenic roles. 2021, 129-158. https://doi.org/10.1016/B978-0-323-85707-9.00001-0
    95. Lauren J. Rice, Heath Ecroyd, Antoine M. van Oijen. Illuminating amyloid fibrils: Fluorescence-based single-molecule approaches. Computational and Structural Biotechnology Journal 2021, 19 , 4711-4724. https://doi.org/10.1016/j.csbj.2021.08.017
    96. Mohammad Salehi, Maryam Nikkhah, Soheila Mohammadi, Saman Hosseinkhani. Transient transfection of WT-αS and A53T-αS brought about a mild apoptosis due to degradation of released cytochrome c through PARC. International Journal of Biological Macromolecules 2021, 166 , 374-384. https://doi.org/10.1016/j.ijbiomac.2020.10.196
    97. Kathryn Sánchez, Kathleen Maguire-Zeiss. MMP13 Expression Is Increased Following Mutant α-Synuclein Exposure and Promotes Inflammatory Responses in Microglia. Frontiers in Neuroscience 2020, 14 https://doi.org/10.3389/fnins.2020.585544
    98. Samra Hasan, Aabgeena Naeem. Consequence of macromolecular crowding on aggregation propensity and structural stability of haemoglobin under glycating conditions. International Journal of Biological Macromolecules 2020, 162 , 1044-1053. https://doi.org/10.1016/j.ijbiomac.2020.06.127
    99. Yang Shen, Wubin Zheng, Yusi Yao, Dongmei Wang, Guanglei Lv, Chunxia Li. Phenoxazine‐based Near‐infrared Fluorescent Probes for the Specific Detection of Copper (II) Ions in Living Cells. Chemistry – An Asian Journal 2020, 15 (18) , 2864-2867. https://doi.org/10.1002/asia.202000783
    100. Feng He, Guangjian Qi, Qian Zhang, Hongwei Cai, Tongxia Li, Ming Li, Qiaofeng Zhang, Jingyu Chen, Jie Ming, Bo Tian, Pei Zhang. Quantitative Phosphoproteomic Analysis in Alpha-Synuclein Transgenic Mice Reveals the Involvement of Aberrant p25/Cdk5 Signaling in Early-stage Parkinson’s Disease. Cellular and Molecular Neurobiology 2020, 40 (6) , 897-909. https://doi.org/10.1007/s10571-019-00780-7
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