Journal of Movement Disorders

Review Articles

α-Synuclein: A Promising Biomarker for Parkinson’s Disease and Related Disorders: Taku Hatano, Ayami Okuzumi, Gen Matsumoto, Tsunemi Taiji, Nobutaka Hattori; Received March 22, 2024 Accepted April 9, 2024 Published online April 9, 2024; DOI: https://doi.org/10.14802/jmd.24075 [Accepted]

458 View
100 Download

Abstract PDF: Mutations in the SNCA gene, which encodes α-synuclein (α-syn), play a key role in the development of genetic Parkinson’s disease (PD). α-Syn is a major component of Lewy bodies in PD and glial cytoplasmic inclusions in multiple system atrophy (MSA). Rapid eye movement sleep behavior disorder (RBD) patients often progress to PD, dementia with Lewy bodies (DLB), or MSA, collectively known as α-synucleinopathies. The loss of dopaminergic neurons with Lewy bodies precedes motor dysfunction in these diseases, but the mechanisms of neurodegeneration due to α-syn aggregation are poorly understood. Monitoring α-syn aggregation in vivo could serve as a diagnostic biomarker and help elucidate the pathogenesis, necessitating a simple and accurate detection method. Seed amplification assays (SAAs), such as real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA), are used to detect small amounts of abnormally structured α-syn protofibrils, which are central to aggregation. These methods are promising for the early diagnosis of α-synucleinopathy. Differences in α-syn filament structures between α-synucleinopathies, observed through transmission electron microscopy and cryo-electron microscopy, suggest their role in the pathogenesis of neurodegeneration. SAAs may differentiate between subtypes of α-synucleinopathy and other diseases. Efforts are also being made to identify α-syn from blood using various methods. This review introduces body fluid α-syn biomarkers based on pathogenic α-syn seeds, which are expected to redefine α-synucleinopathy diagnosis and staging, improving clinical research accuracy and facilitating biomarker development.

Ultrastructures of α-Synuclein Filaments in Synucleinopathy Brains and Experimental Models: Airi Tarutani, Masato Hasegawa; J Mov Disord. 2024;17(1):15-29. Published online November 22, 2023; DOI: https://doi.org/10.14802/jmd.23213

1,356 View
152 Download

Abstract PDF: Intracellular α-synuclein (α-syn) inclusions are a neuropathological hallmark of Lewy body disease (LBD) and multiple system atrophy (MSA), both of which are termed synucleinopathies. LBD is defined by Lewy bodies and Lewy neurites in neurons, while MSA displays glial cytoplasmic inclusions in oligodendrocytes. Pathological α-syn adopts an ordered filamentous structure with a 5–10 nm filament diameter, and this conformational change has been suggested to be involved in the disease onset and progression. Synucleinopathies also exhibit characteristic ultrastructural and biochemical properties of α-syn filaments, and α-syn strains with distinct conformations have been identified. Numerous experimental studies have supported the idea that pathological α-syn self-amplifies and spreads throughout the brain, during which processes the conformation of α-syn filaments may drive the disease specificity. In this review, we summarize the ultrastructural features and heterogeneity of α-syn filaments in the brains of patients with synucleinopathy and in experimental models of seeded α-syn aggregation.

Brief communication

Sensitivity of Detecting Alpha-Synuclein Accumulation in the Gastrointestinal Tract and Tissue Volume Examined: Chaewon Shin, Seong-Ik Kim, Sung-Hye Park, Jung Hwan Shin, Chan Young Lee, Han-Kwang Yang, Hyuk-Joon Lee, Seong-Ho Kong, Yun-Suhk Suh, Han-Joon Kim, Beomseok Jeon; J Mov Disord. 2022;15(3):264-268. Published online July 26, 2022; DOI: https://doi.org/10.14802/jmd.22042

2,709 View
99 Download
1 Crossref

Abstract PDF Supplementary Material

Objective
This study aimed to evaluate whether a larger tissue volume increases the sensitivity of detecting alpha-synuclein (AS) pathology in the gastrointestinal (GI) tract.
Methods
Nine patients with Parkinson’s disease (PD) or idiopathic rapid eye movement sleep disorder (iRBD) who underwent GI operation and had full-depth intestinal blocks were included. All patients were selected from our previous study population. A total of 10 slides (5 serial sections from the proximal and distal blocks) per patient were analyzed.
Results
In previous studies, pathologic evaluation revealed phosphorylated AS (+) in 5/9 patients (55.6%) and in 1/5 controls (20.0%); in this extensive examination, this increased to 8/9 patients (88.9%) but remained the same in controls (20.0%). The severity and distribution of positive findings were similar between patients with iRBD and PD.
Conclusion
Examining a large tissue volume increased the sensitivity of detecting AS accumulation in the GI tract.

Citations

Citations to this article as recorded by

Symmetric and Profound Monoaminergic Degeneration in Parkinson’s Disease with Premotor REM Sleep Behavior Disorder
Kyung Ah Woo, Han-Joon Kim, Jung Hwan Shin, Kangyoung Cho, Hongyoon Choi, Beomseok Jeon
Journal of Parkinson's Disease.2024; : 1. CrossRef

Review Article

Mechanism of Anti-α-Synuclein Immunotherapy: Jun Sung Lee, Seung-Jae Lee; J Mov Disord. 2016;9(1):14-19. Published online January 25, 2016; DOI: https://doi.org/10.14802/jmd.15059

25,544 View
333 Download
35 Web of Science
35 Crossref

Abstract PDF

Immunization therapy targeting α-synuclein has emerged as a promising approach for Parkinson’s disease and perhaps for other synucleinopathies. Several antibodies have shown therapeutic effects in mouse models of synucleinopathies and have alleviated the pathological and behavioral phenotypes of these mice. The mechanisms through which the immunization therapy works were initially puzzling, especially given that α-synuclein is a typical cytosolic protein. Recent studies, however, suggested that extracellular α-synuclein is an important pathogenic entity, and hence, a target for immunotherapy. Here, we review the literature describing immunization therapy for synucleinopathies in mouse models and provide current thoughts on the potential mechanisms underlying the therapeutic effects of α-synuclein immunotherapy.

Citations

Citations to this article as recorded by

Aggregation-Induced Emission Luminogens: A New Possibility for Efficient Visualization of RNA in Plants
Zheng-Chao Yang, Li-Xiang Zhao, Yu-Qi Sang, Xin Huang, Xuan-Chen Lin, Zhi-Ming Yu
Plants.2024; 13(5): 743. CrossRef
Immunisation with UB-312 in the Thy1SNCA mouse prevents motor performance deficits and oligomeric α-synuclein accumulation in the brain and gut
Jacqui T. Nimmo, Harry Smith, Chang Yi Wang, Jessica L. Teeling, James A. R. Nicoll, Ajay Verma, Jean-Cosme Dodart, Zhi Liu, Feng Lin, Roxana O. Carare
Acta Neuropathologica.2022; 143(1): 55. CrossRef
Autophagy-Related Pathways in Vesicular Unconventional Protein Secretion
Shin Hye Noh, Ye Jin Kim, Min Goo Lee
Frontiers in Cell and Developmental Biology.2022;[Epub] CrossRef
Targeting Macroautophagy as a Therapeutic Opportunity to Treat Parkinson’s Disease
Irene Sanchez-Mirasierra, Saurav Ghimire, Sergio Hernandez-Diaz, Sandra-Fausia Soukup
Frontiers in Cell and Developmental Biology.2022;[Epub] CrossRef
A quantitative systems pharmacology model for simulating OFF-Time in augmentation trials for Parkinson’s disease: application to preladenant
Rachel Rose, Emma Mitchell, Piet Van Der Graaf, Daisuke Takaichi, Jun Hosogi, Hugo Geerts
Journal of Pharmacokinetics and Pharmacodynamics.2022; 49(6): 593. CrossRef
Neuroimmune crosstalk and evolving pharmacotherapies in neurodegenerative diseases
Falguni Baidya, Mariya Bohra, Aishika Datta, Deepaneeta Sarmah, Birva Shah, Priya Jagtap, Swapnil Raut, Ankan Sarkar, Upasna Singh, Kiran Kalia, Anupom Borah, Xin Wang, Kunjan R. Dave, Dileep R. Yavagal, Pallab Bhattacharya
Immunology.2021; 162(2): 160. CrossRef
Electrogastrography for diagnosis of early-stage Parkinson's disease
Nobuyuki Araki, Yoshitaka Yamanaka, Anupama Poudel, Yoshikatsu Fujinuma, Akira Katagiri, Satoshi Kuwabara, Masato Asahina
Parkinsonism & Related Disorders.2021; 86: 61. CrossRef
Natural Alkaloid Compounds as Inhibitors for Alpha-Synuclein Seeded Fibril Formation and Toxicity
Simona S. Ghanem, Hend S. Fayed, Qi Zhu, Jia-Hong Lu, Nishant N. Vaikath, Janarthanan Ponraj, Said Mansour, Omar M. A. El-Agnaf
Molecules.2021; 26(12): 3736. CrossRef
Tat-p27 Ameliorates Neuronal Damage Reducing α-Synuclein and Inflammatory Responses in Motor Neurons After Spinal Cord Ischemia
Woosuk Kim, Hyun Jung Kwon, Hyo Young Jung, Kyu Ri Hahn, Seung Myung Moon, Yeo Sung Yoon, In Koo Hwang, Soo Young Choi, Dae Won Kim
Neurochemical Research.2021; 46(12): 3123. CrossRef
Immunotherapies for Parkinson’s Disease: Progression of Clinical Development
Jet Shee Teng, Yin Yin Ooi, Soi Moi Chye, Anna Pick Kiong Ling, Rhun Yian Koh
CNS & Neurological Disorders - Drug Targets.2021; 20(9): 802. CrossRef
Parkinson Disease: Translating Insights from Molecular Mechanisms to Neuroprotection
Sheila K. Pirooznia, Liana S. Rosenthal, Valina L. Dawson, Ted M. Dawson, Eric Barker
Pharmacological Reviews.2021; 73(4): 1204. CrossRef
Anti-inflammatory and Neuroprotective Agents in Clinical Trials for CNS Disease and Injury: Where Do We Go From Here?
Khalil Mallah, Christine Couch, Davis M. Borucki, Amer Toutonji, Mohammed Alshareef, Stephen Tomlinson
Frontiers in Immunology.2020;[Epub] CrossRef
Targeting α-synuclein by PD03 AFFITOPE® and Anle138b rescues neurodegenerative pathology in a model of multiple system atrophy: clinical relevance
Miguel Lemos, Serena Venezia, Violetta Refolo, Antonio Heras-Garvin, Sabine Schmidhuber, Armin Giese, Andrei Leonov, Sergey Ryazanov, Christian Griesinger, Gergana Galabova, Guenther Staffler, Gregor Karl Wenning, Nadia Stefanova
Translational Neurodegeneration.2020;[Epub] CrossRef
Insights Into Peptide Inhibition of Alpha-Synuclein Aggregation
James H. Torpey, Richard M. Meade, Ravina Mistry, Jody M. Mason, Jillian Madine
Frontiers in Neuroscience.2020;[Epub] CrossRef
Novel antibodies detect additional α-synuclein pathology in synucleinopathies: potential development for immunotherapy
Jacqui T. Nimmo, Ajay Verma, Jean-Cosme Dodart, Chang Yi Wang, Jimmy Savistchenko, Ronald Melki, Roxana O. Carare, James A. R. Nicoll
Alzheimer's Research & Therapy.2020;[Epub] CrossRef
Cellular and Molecular Aspects of Parkinson Treatment: Future Therapeutic Perspectives
Khosro Jamebozorgi, Eskandar Taghizadeh, Daryoush Rostami, Hosein Pormasoumi, George E. Barreto, Seyed Mohammad Gheibi Hayat, Amirhossein Sahebkar
Molecular Neurobiology.2019; 56(7): 4799. CrossRef
The Associations between Immunological Reactivity to the Haptenation of Unconjugated Bisphenol A to Albumin and Protein Disulfide Isomerase with Alpha-Synuclein Antibodies
Datis Kharrazian, Martha Herbert, Aristo Vojdani
Toxics.2019; 7(2): 26. CrossRef
Effects of single and combined immunotherapy approach targeting amyloid β protein and α‐synuclein in a dementia with Lewy bodies–like model
Markus Mandler, Edward Rockenstein, Cassia Overk, Michael Mante, Jazmin Florio, Anthony Adame, Changyoun Kim, Radmila Santic, Achim Schneeberger, Frank Mattner, Sabine Schmidhuber, Gergana Galabova, Brian Spencer, Eliezer Masliah, Robert A. Rissman
Alzheimer's & Dementia.2019; 15(9): 1133. CrossRef
Translational therapies for multiple system atrophy: Bottlenecks and future directions
Nadia Stefanova
Autonomic Neuroscience.2018; 211: 7. CrossRef
Integrin CD11b mediates α-synuclein-induced activation of NADPH oxidase through a Rho-dependent pathway
Liyan Hou, Xiuqi Bao, Caixia Zang, Hanyu Yang, Fuqiang Sun, Yuning Che, Xuefei Wu, Shao Li, Dan Zhang, Qingshan Wang
Redox Biology.2018; 14: 600. CrossRef
Serum titers of autoantibodies against α-synuclein and tau in child- and adulthood
Isabell Kuhn, Tobias Rogosch, Theresa I. Schindler, Björn Tackenberg, Michael Zemlin, Rolf F. Maier, Richard Dodel, Yannick Kronimus
Journal of Neuroimmunology.2018; 315: 33. CrossRef
Beneficial Effects of Flavonoids Against Parkinson's Disease
Un Ju Jung, Sang Ryong Kim
Journal of Medicinal Food.2018; 21(5): 421. CrossRef
Unconventional protein secretion – new insights into the pathogenesis and therapeutic targets of human diseases
Jiyoon Kim, Heon Yung Gee, Min Goo Lee
Journal of Cell Science.2018;[Epub] CrossRef
Region-Specific Effects of Immunotherapy With Antibodies Targeting α-synuclein in a Transgenic Model of Synucleinopathy
Martin Kallab, Marcos Herrera-Vaquero, Malin Johannesson, Fredrik Eriksson, Jessica Sigvardson, Werner Poewe, Gregor K. Wenning, Eva Nordström, Nadia Stefanova
Frontiers in Neuroscience.2018;[Epub] CrossRef
Gene therapy for neurological disorders: progress and prospects
Benjamin E. Deverman, Bernard M. Ravina, Krystof S. Bankiewicz, Steven M. Paul, Dinah W. Y. Sah
Nature Reviews Drug Discovery.2018; 17(9): 641. CrossRef
Combined Active Humoral and Cellular Immunization Approaches for the Treatment of Synucleinopathies
Edward Rockenstein, Gary Ostroff, Fusun Dikengil, Florentina Rus, Michael Mante, Jazmin Florio, Anthony Adame, Ivy Trinh, Changyoun Kim, Cassia Overk, Eliezer Masliah, Robert A. Rissman
The Journal of Neuroscience.2018; 38(4): 1000. CrossRef
Holocranohistochemistry enables the visualization of α-synuclein expression in the murine olfactory system and discovery of its systemic anti-microbial effects
Julianna J. Tomlinson, Bojan Shutinoski, Li Dong, Fanyi Meng, Dina Elleithy, Nathalie A. Lengacher, Angela P. Nguyen, Greg O. Cron, Qiubo Jiang, Erik D. Roberson, Robert L. Nussbaum, Nour K. Majbour, Omar M. El-Agnaf, Steffany A. Bennett, Diane C. Lagace,
Journal of Neural Transmission.2017; 124(6): 721. CrossRef
Structure, Distribution, and Genetic Profile of α-Synuclein and Their Potential Clinical Application in Parkinson’s Disease
Xiaoli Si, Jiali Pu, Baorong Zhang
Journal of Movement Disorders.2017; 10(2): 69. CrossRef
Membrane Trafficking Illuminates a Path to Parkinson’s Disease
Takafumi Hasegawa, Naoto Sugeno, Akio Kikuchi, Toru Baba, Masashi Aoki
The Tohoku Journal of Experimental Medicine.2017; 242(1): 63. CrossRef
Decelerated neurodegeneration after intravitreal injection of α-synuclein antibodies in a glaucoma animal model
J. Teister, F. Anders, S. Beck, S. Funke, H. von Pein, V. Prokosch, N. Pfeiffer, F. Grus
Scientific Reports.2017;[Epub] CrossRef
Impact of aging immune system on neurodegeneration and potential immunotherapies
Zhanfeng Liang, Yang Zhao, Linhui Ruan, Linnan Zhu, Kunlin Jin, Qichuan Zhuge, Dong-Ming Su, Yong Zhao
Progress in Neurobiology.2017; 157: 2. CrossRef
A novel panel of α-synuclein antibodies reveal distinctive staining profiles in synucleinopathies
Jess-Karan S. Dhillon, Cara Riffe, Brenda D. Moore, Yong Ran, Paramita Chakrabarty, Todd E. Golde, Benoit I. Giasson, Stephan N. Witt
PLOS ONE.2017; 12(9): e0184731. CrossRef
Vaccination strategies in tauopathies and synucleinopathies
Anne K. Braczynski, Jörg B. Schulz, Jan‐Philipp Bach
Journal of Neurochemistry.2017; 143(5): 467. CrossRef
Missions of <italic>Journal of Movement Disorders</italic>
Yun Joong Kim
Journal of Movement Disorders.2016; 9(1): 1. CrossRef
How strong is the evidence that Parkinson's disease is a prion disorder?
Patrik Brundin, Jiyan Ma, Jeffrey H. Kordower
Current Opinion in Neurology.2016; 29(4): 459. CrossRef

First
Prev
Page of 1
Next
Last

Search