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  Suppressing Tau Aggregation and Toxicity by an Anti-Aggregant Tau Fragment.

Pir, G. J., Choudhary, B., Kaniyappan, S., Chandupatla, R. R., Mandelkow, E., Mandelkow, E.-M., et al. (2019). Suppressing Tau Aggregation and Toxicity by an Anti-Aggregant Tau Fragment. Molecular Neurobiology, 56(5), 3751-3767. doi:10.1007/s12035-018-1326-z.

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Pir, Ghulam Jeelani1, Author
Choudhary, Bikash1, Author
Kaniyappan, Senthilvelrajan1, Author
Chandupatla, Ram Reddy1, Author
Mandelkow, E2, Author           
Mandelkow, Eva-Maria2, Author           
Wang, Yipeng1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Neuronal Cytoskeleton and Alzheimer's Disease, Cooperations, Center of Advanced European Studies and Research (caesar), Max Planck Society, Ludwig-Erhard-Allee 2, 53175 Bonn, DE, ou_2173677              

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Free keywords: Aggregation; Alzheimer disease; Cell model; Life-span; Microtubules; Tau; Transgenic C.elegans; β-breaker peptides
 Abstract: Tau aggregation is a hallmark of a group of neurodegenerative diseases termed Tauopathies. Reduction of aggregation-prone Tau has emerged as a promising therapeutic approach. Here, we show that an anti-aggregant Tau fragment (F3ΔKPP, residues 258-360) harboring the ΔK280 mutation and two proline substitutions (I277P & I308P) in the repeat domain can inhibit aggregation of Tau constructs in vitro, in cultured cells and in vivo in a Caenorhabditis elegans model of Tau aggregation. The Tau fragment reduced Tau-dependent cytotoxicity in a N2a cell model, suppressed the Tau-mediated neuronal dysfunction and ameliorated the defective locomotion in C. elegans. In vitro the fragment competes with full-length Tau for polyanionic aggregation inducers and thus inhibits Tau aggregation. Our combined in vitro and in vivo results suggest that the anti-aggregant Tau fragment may potentially be used to address the consequences of Tau aggregation in Tauopathies.

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Language(s): eng - English
 Dates: 2018-09-082019-05
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 30196394
DOI: 10.1007/s12035-018-1326-z
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Title: Molecular Neurobiology
  Other : Mol. Neurobiol.
Source Genre: Journal
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Publ. Info: Clifton, NJ : Humana Press
Pages: - Volume / Issue: 56 (5) Sequence Number: - Start / End Page: 3751 - 3767 Identifier: ISSN: 0893-7648
CoNE: https://pure.mpg.de/cone/journals/resource/954925558500