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Fresh evidence for major brain gangliosides as a target for the treatment of Alzheimer's disease.

Abstract：

:Although it was suggested that gangliosides play an important role in the binding of amyloid fragments to neuronal cells, the exact role of gangliosides in Alzheimer's disease (AD) pathology remains unclear. To understand the role of gangliosides in AD pathology in vivo, we crossed st3gal5-deficient (ST3-/-) mice that lack major brain gangliosides GM1, GD1a, GD3, GT1b, and GQ1b with 5XFAD transgenic mice that overexpress 3 mutant human amyloid proteins AP695 and 2 presenilin PS1 genes. We found that ST3-/- 5XFAD mice have a significantly reduced burden of amyloid depositions, low level of neuroinflammation, and did not exhibit neuronal loss or synaptic dysfunction. ST3-/- 5XFAD mice performed significantly better in a cognitive test than wild-type (WT) 5XFAD mice, which was comparable with WT nontransgenic mice. Treatment of WT 5XFAD mice with the sialic acid-specific Limax flavus agglutinin resulted in substantial improvement of AD pathology to a level of ST3-/- 5XFAD mice. Thus, our findings highlight an important role for gangliosides as a target for the treatment of AD.

journal_name

Neurobiol Aging

journal_title

Neurobiology of aging

authors

Dukhinova M,Veremeyko T,Yung AWY,Kuznetsova IS,Lau TYB,Kopeikina E,Chan AML,Ponomarev ED

doi

10.1016/j.neurobiolaging.2019.01.020

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

128-143

eissn

0197-4580

issn

1558-1497

pii

S0197-4580(19)30034-X

journal_volume

77

pub_type

杂志文章

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