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
Neurosciences
Sheila M. Fleming, Ashley Davis, Emily Simons
Summary: Parkinson's disease is characterized by the abnormal accumulation of alpha-synuclein in the brain and the loss of dopaminergic neurons. Immunotherapies targeting alpha-synuclein have become a key focus for the development of novel therapies for PD.
Review
Neurosciences
Kreesan Reddy, Birger Victor Dieriks
Summary: This article discusses the evidence for MSA-specific alpha-Syn strains, proposes possible causes for strain formation, and explores the interactions between oligodendrocytes, neurons, and alpha-Syn, as well as the impact of additional variables.
MOLECULAR NEURODEGENERATION
(2022)
Article
Neurosciences
Jay J. Shukla, Nadia Stefanova, Ashley Bush, Gawain McColl, David Finkelstein, Erin J. McAllum
Summary: This study found changes in iron metabolism in different brain regions of aged PLP-alpha syn mice and tested the efficacy of iron-lowering drugs in alleviating disease phenotype in these mice. The results indicated iron accumulation and perturbed iron-ferritin interaction in the substantia nigra, putamen, and cerebellum of aged PLP-alpha syn mice. Additionally, targeting iron in MSA could be a viable therapeutic option as shown by improvements in motor performance and neuronal survival in the study.
NEUROBIOLOGY OF DISEASE
(2021)
Review
Biochemistry & Molecular Biology
Kurt A. Jellinger, Gregor K. Wenning, Nadia Stefanova
Summary: Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disease with a complex clinical presentation. It shares molecular similarities with Parkinson's disease but presents unique pathological features. The debate over whether it should be classified as a prion disease or its potential human transmission remains unresolved.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Sara A. M. Holec, Jisoo Lee, Abby Oehler, Felicia K. Ooi, Daniel A. Mordes, Steven H. Olson, Stanley B. Prusiner, Amanda L. Woerman
Summary: This study demonstrates that MSA prions can transmit neurological disease to mice expressing wild-type SNCA in a sex-dependent manner. The transmission of MSA prions shows distinct biological activities compared to the transmission of WT preformed fibrils.
ACTA NEUROPATHOLOGICA
(2022)
Article
Clinical Neurology
John Stephen Middleton, Hanna Lynn Hovren, Nelson Kha, Manuel Joseph Medina, Karen Ruth MacLeod, Luis Concha-Marambio, Kendal Jay Jensen
Summary: Parkinson's disease (PD) can be misdiagnosed due to its clinical overlap with atypical parkinsonism. The a-Synuclein (aSyn) Seed Amplification Assay (SAA) has been reported as a potential diagnostic indicator for PD, but its use as a clinical laboratory test has not been validated. This study compares the accuracy of PD clinical diagnosis using the aSyn-SAA test with two different diagnostic inclusion criteria, showing a significant improvement when combined with confirmatory imaging.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Margaux Teil, Sandra Dovero, Mathieu Bourdenx, Marie-Laure Arotcarena, Sandrine Camus, Gregory Porras, Marie-Laure Thiolat, Ines Trigo-Damas, Celine Perier, Cristina Estrada, Nuria Garcia-Carrillo, Michele Morari, Wassilios G. Meissner, Maria Trinidad Herrero, Miquel Vila, Jose A. Obeso, Erwan Bezard, Benjamin Dehay
Summary: Synucleinopathies, including Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, are characterized by the deposit of alpha-synuclein aggregates in neurons and glial cells. A study found that inoculating brain fractions containing glial cytoplasmic inclusions from multiple system atrophy patients into non-human primates resulted in neurodegeneration, oligodendrocyte loss, demyelination, neuroinflammation and alpha-synuclein pathology. These findings suggest the potential use of this experimental model for multiple system atrophy research and therapy development.
Article
Clinical Neurology
An Cheng, Ichiro Kawahata, Yifei Wang, Wenbin Jia, Haoyang Wang, Tomoki Sekimori, Yi Chen, Hiroyoshi Suzuki, Atsushi Takeda, Nadia Stefanova, David Finkelstein, Wenbo Ma, Min Chen, Takuya Sasaki, Kohji Fukunaga
Summary: Multiple system atrophy (MSA) is a neurodegenerative disease characterized by accumulation of misfolded a-synuclein (aSyn) and myelin disruption. This study identified epsin-2 as a potential regulator of aSyn propagation in MSA brains, suggesting epsin-2 as a novel therapeutic target for MSA.
Article
Clinical Neurology
Yasuo Miki, Kunikazu Tanji, Kana Shinnai, Makoto T. Tanaka, Firat Altay, Sandrine C. Foti, Catherine Strand, Takanori Sasaki, Tomoya Kon, Shuji Shimoyama, Tomonori Furukawa, Haruo Nishijima, Hiromi Yamazaki, Yasmine T. Asi, Conceicao Bettencourt, Zane Jaunmuktane, Mari Tada, Fumiaki Mori, Hiroki Mizukami, Masahiko Tomiyama, Hilal A. Lashuel, Tammaryn Lashley, Akiyoshi Kakita, Helen Ling, Andrew J. Lees, Janice L. Holton, Thomas T. Warner, Koichi Wakabayashi
Summary: This study investigated how abnormal alpha-synuclein in the hippocampus leads to memory impairment in multiple system atrophy (MSA). The results suggest that increased alpha-synuclein oligomers may be a pathological cause of memory impairment in MSA.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2022)
Review
Clinical Neurology
Meghana Goolla, William P. Cheshire, Owen A. Ross, Naveen Kondru
Summary: Multiple system atrophy (MSA) is a rare and progressive neurodegenerative disorder that is challenging to diagnose accurately and early. Current diagnostic methods have limitations in sensitivity and specificity, but recent advances in molecular biomarker research offer hope for improving MSA diagnosis.
FRONTIERS IN NEUROLOGY
(2023)
Article
Clinical Neurology
Takashi Ando, Yuichi Riku, Akio Akagi, Hiroaki Miyahara, Mitsuaki Hirano, Toshimasa Ikeda, Hiroyuki Yabata, Ryuichi Koizumi, Chisato Oba, Saori Morozumi, Keizo Yasui, Atsuko Goto, Taiji Katayama, Satoko Sakakibara, Ikuko Aiba, Motoko Sakai, Masaaki Konagaya, Keiko Mori, Yasuhiro Ito, Hiroyuki Yuasa, Masayo Nomura, Kristine Joyce L. Porto, Jun Mitsui, Shoji Tsuji, Maya Mimuro, Yoshio Hashizume, Masahisa Katsuno, Yasushi Iwasaki, Mari Yoshida
Summary: In this study, MSA patients with prominent hippocampal involvement showed specific demographic and clinical characteristics. The severe hippocampal pathology seen in these patients suggests a potential pathological variant of MSA characterized by neuronal alpha-synucleinopathy.
Review
Cell Biology
Jen-Hsiang T. Hsiao, Onur Tanglay, Anne A. Li, Aysha Y. G. Strobbe, Woojin Scott Kim, Glenda M. Halliday, YuHong Fu
Summary: Multiple system atrophy (MSA) is a debilitating movement disorder with unknown etiology. It presents with characteristic parkinsonism and/or cerebellar dysfunction due to deterioration in specific brain regions. The early pathological events and development mechanisms of MSA are reviewed, focusing on the involvement of oligodendrocyte lineage cells and alpha-synuclein. This understanding will guide future research in MSA.
Article
Neurosciences
Ivan Martinez-Valbuena, Naomi P. Visanji, Ain Kim, Heather H. C. Lau, Raphaella W. L. So, Sohaila Alshimemeri, Andrew Gao, Michael A. Seidman, Maria R. Luquin, Joel C. Watts, Anthony E. Lang, Gabor G. Kovacs
Summary: This study revealed significant differences in the seeding activity of alpha-synuclein in the brains of patients with Multiple System Atrophy (MSA), as well as regional variations within individual brains. These findings provide important experimental groundwork for future subclassification and rapid diagnostic assays for MSA.
TRANSLATIONAL NEURODEGENERATION
(2022)
Review
Biochemistry & Molecular Biology
Chisato Kinoshita, Noriko Kubota, Koji Aoyama
Summary: Multiple system atrophy is a rare neurodegenerative disease that is characterized by oxidative stress, glutathione deficiency, and dysregulation of miRNA. These factors are closely related to the pathology of MSA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)