Repository logo

Infoscience

  • English
  • French
Log In
Logo EPFL, École polytechnique fédérale de Lausanne

Infoscience

  • English
  • French
Log In
  1. Home
  2. Academic and Research Output
  3. Journal articles
  4. Novel therapeutic strategy for neurodegeneration by blocking Aβ seeding mediated aggregation in models of Alzheimer's disease
 
Loading...
Thumbnail Image
research article

Novel therapeutic strategy for neurodegeneration by blocking Aβ seeding mediated aggregation in models of Alzheimer's disease

Eleuteri, Simona
•
Di Giovanni, Saviana
•
Rockenstein, Edward
Show more
2015
Neurobiology of disease

Aβ accumulation plays a central role in the pathogenesis of Alzheimer's disease (AD). Recent studies suggest that the process of Aβ nucleated polymerization is essential for Aβ fibril formation, pathology spreading and toxicity. Therefore, targeting this process represents an effective therapeutic strategy to slow or block disease progression. To discover compounds that might interfere with the Aβ seeding capacity, toxicity and pathology spreading, we screened a focused library of FDA-approved drugs in vitro using a seeding polymerization assay and identified small molecule inhibitors that specifically interfered with Aβ seeding-mediated fibril growth and toxicity. Mitoxantrone, bithionol and hexachlorophene were found to be the strongest inhibitors of fibril growth and protected primary cortical neuronal cultures against Aβ-induced toxicity. Next, we assessed the effects of these three inhibitors in vivo in the mThy1-APPtg mouse model of AD (8-month-old mice). We found that mitoxantrone and bithionol, but not hexachlorophene, stabilized diffuse amyloid plaques, reduced the levels of Aβ42 oligomers and ameliorated synapse loss, neuronal damage and astrogliosis. Together, our findings suggest that targeting fibril growth and Aβ seeding capacity constitutes a viable and effective strategy for protecting against neurodegeneration and disease progression in AD.

  • Details
  • Metrics
Type
research article
DOI
10.1016/j.nbd.2014.08.017
Web of Science ID

WOS:000349655900015

Author(s)
Eleuteri, Simona
•
Di Giovanni, Saviana
•
Rockenstein, Edward
•
Mante, Mike
•
Adame, Antony
•
Trejo, Margarita
•
Wrasidlo, Wolf
•
Wu, Fang  
•
Fraering, Patrick C
•
Masliah, Eliezer
Show more
Date Issued

2015

Published in
Neurobiology of disease
Volume

74

Start page

144

End page

57

Peer reviewed

NON-REVIEWED

Written at

EPFL

EPFL units
LMNN  
CMSN  
Available on Infoscience
November 17, 2014
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/108904
Logo EPFL, École polytechnique fédérale de Lausanne
  • Contact
  • infoscience@epfl.ch

  • Follow us on Facebook
  • Follow us on Instagram
  • Follow us on LinkedIn
  • Follow us on X
  • Follow us on Youtube
AccessibilityLegal noticePrivacy policyCookie settingsEnd User AgreementGet helpFeedback

Infoscience is a service managed and provided by the Library and IT Services of EPFL. © EPFL, tous droits réservés