Tau oligomers mediate α-synuclein toxicity and can be targeted by immunotherapy

J.E. Gerson, K.M. Farmer, N. Henson, D.L. Castillo-Carranza, M. Carretero Murillo, U. Sengupta, A. Barrett, R. Kayed

Resultado de la investigaciónrevisión exhaustiva

30 Citas (Scopus)

Resumen

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Idioma originalEnglish
PublicaciónMolecular Neurodegeneration
Volumen13
N.º1
DOI
EstadoPublished - 15 mar 2018
Publicado de forma externa

All Science Journal Classification (ASJC) codes

  • Biología molecular
  • Neurología clínica
  • Neurociencia celular y molecular

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