Article
Multidisciplinary Sciences
Tae-In Kam, Hyejin Park, Shih-Ching Chou, Jonathan G. Van Vranken, Melanie J. Mittenbuhler, Hyeonwoo Kim, A. Mu, Yu Ree Choi, Devanik Biswas, Justin Wang, Yu Shin, Alexis Loder, Senthilkumar S. Karuppagounder, Christiane D. Wrann, Valina L. Dawson, Bruce M. Spiegelman, Ted M. Dawson
Summary: This study shows that irisin can prevent neurodegeneration caused by pathological alpha-synuclein in Parkinson's disease, and it also reduces motor deficits. Irisin functions by enhancing endolysosomal degradation of pathologic alpha-synuclein.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Aitor Franco, Pablo Gracia, Adai Colom, Jose D. Camino, Jose Angel Fernandez-Higuero, Natalia Orozco, Alexander Dulebo, Leonor Saiz, Nunilo Cremades, Jose M. G. Vilar, Adelina Prado, Arturo Muga
Summary: Research shows that the Hsc70-based disaggregase system preferentially breaks down toxic oligomers and short fibrils, while its activity against larger, less toxic amyloids is severely impaired. This behavior is the result of an all-or-none abrupt solubilization of individual aggregates.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Samanta Mazzetti, Alessandra M. Calogero, Gianni Pezzoli, Graziella Cappelletti
Summary: This paragraph discusses the interplay between alpha-synuclein and the microtubule cytoskeleton in neurodegenerative diseases. Alpha-synuclein is a key protein involved in neurodegeneration, and its interaction with other proteins and structures makes it difficult to identify the trigger for neuronal death. The imbalance of the microtubule cytoskeleton is emerging as a convergence point in neurodegeneration. Alpha-synuclein and microtubules have been shown to interact and communicate with other intracellular structures.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Neurosciences
Jun Zhao, Buyan Pan, Marie Fina, Yun Huang, Marie Shimogawa, Kelvin C. Luk, Elizabeth Rhoades, E. James Petersson, Dawei W. Dong, Anna Kashina
Summary: In this study, the arginylation of alpha-synuclein (alpha-syn) was found to occur at two sites, E46 and E83, in human brain tissue. The level of arginylation was inversely correlated with overall alpha-syn levels and patient age, suggesting a potential neuroprotective role of alpha-syn arginylation in preventing abnormal accumulation during neurodegeneration and aging in the human brain.
TRANSLATIONAL NEURODEGENERATION
(2022)
Article
Multidisciplinary Sciences
Jared T. Hinkle, Jaimin Patel, Nikhil Panicker, Senthilkumar S. Karuppagounder, Devanik Biswas, Bonn Belingon, Rong Chen, Saurav Brahmachari, Olga Pletnikova, Juan C. Troncoso, Valina L. Dawson, Ted M. Dawson
Summary: This study reveals that pathological alpha Syn aggregates in idiopathic Parkinson's disease can cause STING-dependent neuroinflammation and dopaminergic neurodegeneration. Microglial STING activation plays a crucial role in the development of alpha-synudeinopathies, including Parkinson's disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Medicine, Research & Experimental
Marc Emmenegger, Elena De Cecco, Marian Hruska-Plochan, Timo Eninger, Matthias M. Schneider, Melanie Barth, Elena Tantardini, Pierre de Rossi, Mehtap Bacioglu, Rebekah G. Langston, Alice Kaganovich, Nora Bengoa-Vergniory, Andres Gonzalez-Guerra, Merve Avar, Daniel Heinzer, Regina Reimann, Lisa M. Haesler, Therese W. Herling, Naunehal S. Matharu, Natalie Landeck, Kelvin Luk, Ronald Melki, Philipp J. Kahle, Simone Hornemann, Tuomas P. J. Knowles, Mark R. Cookson, Magdalini Polymenidou, Mathias Jucker, Adriano Aguzzi
Summary: The expression pattern of LAG3 in human and mouse brains was analyzed, with no evidence of neurons expressing LAG3. While LAG3 was confirmed to interact with alpha-synuclein fibrils, the specificity of this interaction appears limited. Additionally, overexpression of LAG3 did not worsen alpha-synuclein pathology.
EMBO MOLECULAR MEDICINE
(2021)
Article
Neurosciences
Dylan J. Dues, Yue Ma, An Phu Tran Nguyen, Alina Offerman, Ian Beddows, Darren J. Moore
Summary: Leucine-rich repeat kinase 2 (LRRK2) and alpha-synuclein play important roles in the pathobiology of Parkinson's disease (PD), but the interaction between LRRK2 and alpha-synuclein in the accumulation of pathological alpha-synuclein remains unclear. Through experiments, it was found that LRRK2 does not have a significant impact on alpha-synuclein pathology in the mouse forebrain, but may contribute to alpha-synuclein-induced neuroinflammation.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Mustafa T. Ardah, Nabil Eid, Tohru Kitada, M. Emdadul Haque
Summary: Parkinson's disease is characterized by dopamine neuron loss and protein misfolding. The polyphenol Ellagic acid can reduce α-syn aggregation and toxicity, enhance cell viability by activating autophagy and suppressing apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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
Clinical Neurology
Teresa Torre-Muruzabal, Anke van der Perren, Audrey Coens, Geraldine Gelders, Anna Barber Janer, Sara Camacho-Garcia, Therese Klingstedt, Peter Nilsson, Nadia Stefanova, Ronald Melki, Veerle Baekelandt, Wouter Peelaerts
Summary: This study found that the progression of multiple system atrophy is influenced by different types of alpha Syn strains. Alpha Syn strains impact disease progression through oligodendroglial, neurotoxic, and immune-related mechanisms, leading to neurodegeneration and brain atrophy. The activation of microglial cells is associated with the structural features of alpha Syn strains.
Article
Cell Biology
Lea Elsholz, Yasmine Wasser, Patrick Ziegler, Pardes Habib, Aaron Voigt
Summary: Inhibiting CK1 kinase activity by overexpressing CK1 binding protein (CK1BP) can reduce S129 phosphorylation, oligomerization, and insoluble accumulation of alpha-Syn. The results suggest that CK1BP may have beneficial effects on neurodegenerative diseases and represents a promising target for therapeutic approaches against alpha-synucleinopathies.
Article
Neurosciences
Brent J. Ryan, Nora Bengoa-Vergniory, Matthew Williamson, Ecem Kirkiz, Rosalind Roberts, Gabriele Corda, Maximilian Sloan, Saba Saqlain, Marta Cherubini, Josse Poppinga, Helle Bogtofte, Milena Cioroch, Svenja Hester, Richard Wade-Martins
Summary: The accumulation of alpha-synuclein oligomers leads to dopaminergic neuronal-specific dysfunction through mitochondrial toxicity, which can be attenuated by REST in an early model of Parkinsonian pathology. This finding highlights REST as a mediator of dopaminergic vulnerability in Parkinson's disease.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Clinical Neurology
Cheng Jiang, Franziska Hopfner, Daniela Berg, Michele T. Hu, Andrea Pilotto, Barbara Borroni, Jason J. Davis, George K. Tofaris
Summary: The study demonstrates that measuring alpha-synuclein levels above 14 pg/mL in L1CAM-immunocaptured serum exosomes can robustly differentiate Parkinson's disease from other movement disorders. Furthermore, elevated levels of exosomal clusterin in individuals with 4-repeat tauopathies, combined with alpha-synuclein, improves the assay's performance in distinguishing Parkinson's disease from 4-repeat tauopathies. However, correction for the generic exosomal protein syntenin-1 did not consistently enhance the assay's performance.
MOVEMENT DISORDERS
(2021)
Review
Biochemistry & Molecular Biology
Jacob S. Deyell, Manjari Sriparna, Mingyao Ying, Xiaobo Mao
Summary: Synucleinopathies are devastating neurodegenerative diseases characterized by abnormal accumulation of the protein alpha-synuclein. Microglia, the immune cells in the central nervous system, play a crucial role in the pathogenesis of synucleinopathies. They are initially neuroprotective but contribute to further neurodegeneration in chronic disease states. This review highlights the structural varieties of alpha-synuclein, microglial receptor-mediated interactions, cellular recognition and uptake of alpha-synuclein, and downstream effects leading to neuroinflammation and neurodegeneration. Understanding microglial interactions with alpha-synuclein is vital for identifying therapeutic interventions and gauging potential pathways of neurodegeneration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Xin Yuan, Yingxu Yang, Chaoyang Liu, Ye Tian, Danhao Xia, Zehua Liu, Lina Pan, Min Xiong, Jing Xiong, Lanxia Meng, Zhaohui Zhang, Keqiang Ye, Haiqiang Jiang, Zhentao Zhang
Summary: This study reveals that exposure to PM2.5 may have a direct impact on α-Syn pathology and increase the risk for Parkinson's disease. PM2.5 promotes the fibrillization and aggregation of α-Syn, leading to enhanced seeding activity and neurotoxicity of α-Syn fibrils. Additionally, PM2.5 induces mitochondrial dysfunction and oxidative stress.
MOVEMENT DISORDERS
(2022)
Article
Multidisciplinary Sciences
Christopher D. Bennett, Sarah E. Kohe, Simrandip K. Gill, Nigel P. Davies, Martin Wilson, Lisa C. D. Storer, Timothy Ritzmann, Simon M. L. Paine, Ian S. Scott, Ina Nicklaus-Wollenteit, Daniel A. Tennant, Richard G. Grundy, Andrew C. Peet
SCIENTIFIC REPORTS
(2018)
Review
Clinical Neurology
A. Kumaria, H. W. Chan, R. J. Goldspring, S. M. L. Paine, G. R. Dow
Summary: This article reports a case of isolated myxopapillary ependymoma (MPE) of the fourth ventricle, highlighting the importance of exhaustive clinical and radiological investigation for intracranial ependymoma.
BRITISH JOURNAL OF NEUROSURGERY
(2022)
Article
Neurosciences
Anqi Yao, Sarah J. Storr, Khaled Al-hadyan, Ruman Rahman, Stuart Smith, Richard Grundy, Simon Paine, Stewart G. Martin
MOLECULAR NEUROBIOLOGY
(2020)
Article
Oncology
Timothy A. Ritzmann, Hazel A. Rogers, Simon M. L. Paine, Lisa C. D. Storer, Thomas S. Jacques, Rebecca J. Chapman, David Ellison, Andrew M. Donson, Nicholas K. Foreman, Richard G. Grundy
PEDIATRIC BLOOD & CANCER
(2020)
Article
Ophthalmology
Hardeep Singh Mudhar, Tatyana Milman, Ralph C. Eagle, Tracy Sanderson, Leanne Pheasey, Simon Paine, Sachin Salvi, Ian G. Rennie, Paul Rundle, Carol L. Shields, Jerry A. Shields
Summary: PAX8 expression in ocular tissues and tumors shows specific distribution patterns, providing a useful diagnostic marker for adult intraocular tumors. Its staining consistency makes it a valuable addition to diagnostic antibody panels for challenging intraocular neoplasms.
Article
Clinical Neurology
Jessica C. Pickles, Kshitij Mankad, Miren Aizpurua, Simon M. L. Paine, Leslie R. Bridges, Fernando Carceller, Elwira Szychot, Mark Walker, Amy R. Fairchild, Talisa Mistry, Olumide Ogunbiyi, Alice Rolland, Thomas J. Stone, Carryl Dryden, Dilys Addy, Elisa Garimberti, Jane Chalker, Felix Sahm, David T. W. Jones, Darren Hargrave, Thomas S. Jacques
Summary: This study presents three pediatric cases of Diffuse Glioneuronal Tumours with Oligodendroglioma-like features and Nuclear Clusters (DGONC), expanding our understanding of this condition.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Article
Clinical Neurology
R. A. Dineen, C. Blanchard, S. Pszczolkowski, S. Paine, M. Prasad, G. Chow, W. P. Whitehouse, D. P. Auer
Summary: This study found a high prevalence of SWI hypointense lesions in children and young people with ataxia telangiectasia, which accumulate with age starting from 12 years old. These lesions are predominantly located in the supratentorial region and differ from the cerebellar-dominant neurodegeneration typically seen in this condition. Further research is needed to determine the clinical significance of these imaging-detected lesions.
AMERICAN JOURNAL OF NEURORADIOLOGY
(2021)
Article
Clinical Neurology
Yao-Feng Li, Fatma Scerif, Simon R. Picker, Thomas J. Stone, Jessica C. Pickles, Dale A. Moulding, Aimee Avery, Alex Virasami, Amy R. Fairchild, Martin Tisdall, William Harkness, J. Helen Cross, Darren Hargrave, Francois Guillemot, Simon M. Paine, Shireena A. Yasin, Thomas S. Jacques
Summary: This study identified previously uncharacterised small cell populations in FCD and TS, highlighting a new level of diversity and cellular interactions in cortical malformations. The findings provide a generalisable approach to understanding cell-cell interactions and cellular heterogeneity in developmental neuropathology.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Article
Clinical Neurology
Zane Jaunmuktane, Gargi Banerjee, Simon Paine, Adrian Parry-Jones, Peter Rudge, Joan Grieve, Ahmed K. Toma, Simon F. Farmer, Simon Mead, Henry Houlden, David J. Werring, Sebastian Brandner
ACTA NEUROPATHOLOGICA
(2021)
Article
Hematology
Furqaan A. Kaji, Nicolas Martinez-Calle, Mark J. Bishton, Rocio Figueroa, Joanne Adlington, Michael O'Donoghue, Stuart Smith, Paul Byrne, Simon Paine, Vishakha Sovani, Dorothee Auer, Eleanor James, Eric M. Bessell, Matthew J. Grainge, Christopher P. Fox
Summary: Observational study with long-term follow-up of PCNSL patients revealed that treatment with high-dose methotrexate (HD-MTX) and rituximab in recent years has improved survival outcomes. Prompt initiation of chemotherapy has also shown a positive impact on patients' overall survival and progression-free survival.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Meeting Abstract
Oncology
Timothy A. Ritzmann, Rebecca J. Chapman, Donald Macarthur, Conor Mallucci, John-Paul Kilday, Nicola Thorp, Piergiorgio Modena, Marzia Giagnacovo, Rob Dineen, Timothy Jaspan, Kristian W. Pajtler, Thomas S. Jacques, Simon M. L. Paine, David W. Ellison, Eric Bouffet, Richard G. Grundy
Review
Clinical Neurology
Peter Weir, Ashwin Kumaria, Alhassan Mohmed, Shazia Javed, Simon Paine, Paul Byrne
Summary: Beckwith-Wiedemann syndrome (BWS) is a rare congenital overgrowth syndrome that may be associated with certain childhood tumors. This case report presents the first documented case of glioblastoma associated with BWS, and explores similarities in the molecular pathomechanisms of BWS and glioblastoma.
ACTA NEUROCHIRURGICA
(2022)
Article
Clinical Neurology
Ashwin Kumaria, Forsan Jahshan, Simon Paine, Malcolm Reed, Harshal A. Ingale, Yujay Ramakrishnan
Summary: This article presents a rare case of olfactory neuroblastoma originating from the sphenoid sinus, which was successfully treated with surgery and radiotherapy. Complete resection is recommended in ectopic ONB.
BRITISH JOURNAL OF NEUROSURGERY
(2023)
Article
Biotechnology & Applied Microbiology
Eleanor Bishop, Monika Dimitrova, Alexander Froggatt, Maria Estevez-Cebrero, Lisa C. D. Storer, Francis Mussai, Simon Paine, Richard G. Grundy, Madhumita Dandapani
Summary: Despite improvements in treatment and survival for paediatric cancers, brain tumours in children still have poor outcomes. This study investigates the potential of targeting the auxotrophy of extracellular arginine in paediatric brain tumours as a novel therapeutic approach. The results show that multiple types of paediatric brain tumours demonstrate arginine auxotrophy based on protein expression, suggesting that therapeutic arginine depletion may be a useful treatment strategy in these tumours.
BIOMED RESEARCH INTERNATIONAL
(2022)
Article
Biotechnology & Applied Microbiology
Eleanor Bishop, Monika Dimitrova, Alexander Froggatt, Maria Estevez-Cebrero, Lisa C. D. Storer, Francis Mussai, Simon Paine, Richard G. Grundy, Madhumita Dandapani
Summary: The study found that extracellular arginine dependency is common in pediatric brain tumors, showing an auxotrophic signature. This discovery provides a new avenue for using arginine depletion as a treatment strategy.
BIOMED RESEARCH INTERNATIONAL
(2022)