Title |
Tau oligomers mediate α-synuclein toxicity and can be targeted by immunotherapy
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Published in |
Molecular Neurodegeneration, March 2018
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DOI | 10.1186/s13024-018-0245-9 |
Pubmed ID | |
Authors |
Julia E. Gerson, Kathleen M. Farmer, Natalie Henson, Diana L. Castillo-Carranza, Mariana Carretero Murillo, Urmi Sengupta, Alan Barrett, Rakez Kayed |
Abstract |
We have evaluated the efficacy of targeting the toxic, oligomeric form of tau protein by passive immunotherapy in a mouse model of synucleinopathy. Parkinson's disease and Lewy body dementia are two of the most common neurodegenerative disorders and are primarily characterized by the accumulation of α-synuclein in Lewy bodies. However, evidence shows that smaller, oligomeric aggregates are likely the most toxic form of the protein. Moreover, a large body of research suggests that α-synuclein interacts with tau in disease and may act in a synergistic mechanism, implicating tau oligomers as a potential therapeutic target. We treated seven-month-old mice overexpressing mutated α-synuclein (A53T mice) with tau oligomer-specific monoclonal antibody (TOMA) and a control antibody and assessed both behavioral and pathological phenotypes. We found that A53T mice treated with TOMA were protected from cognitive and motor deficits two weeks after a single injection. Levels of toxic tau oligomers were specifically decreased in the brains of TOMA-treated mice. Tau oligomer depletion also protected against dopamine and synaptic protein loss. These results indicate that targeting tau oligomers is beneficial for a mouse model of synucleinopathy and may be a viable therapeutic strategy for treating diseases in which tau and α-synuclein have a synergistic toxicity. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United Kingdom | 1 | 20% |
United States | 1 | 20% |
Spain | 1 | 20% |
Unknown | 2 | 40% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 40% |
Scientists | 2 | 40% |
Science communicators (journalists, bloggers, editors) | 1 | 20% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 90 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Bachelor | 13 | 14% |
Researcher | 12 | 13% |
Student > Ph. D. Student | 11 | 12% |
Student > Master | 7 | 8% |
Student > Postgraduate | 6 | 7% |
Other | 14 | 16% |
Unknown | 27 | 30% |
Readers by discipline | Count | As % |
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Neuroscience | 19 | 21% |
Biochemistry, Genetics and Molecular Biology | 14 | 16% |
Medicine and Dentistry | 8 | 9% |
Agricultural and Biological Sciences | 6 | 7% |
Nursing and Health Professions | 3 | 3% |
Other | 12 | 13% |
Unknown | 28 | 31% |