Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1822, Issue 10, Pages 1629-1637Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbadis.2012.07.003
Keywords
scyllo-Inositol; Alzheimer disease; Amyloid-beta peptide; TgCRND8; Autophagy; Lysosome
Funding
- Canadian Institutes of Health Research [PRG 37857]
- NSERC [CHRP:365537]
- Ontario Postdoctoral Scholarship
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scyllo-Inositol (SI) is an endogenous inositol stereoisomer known to inhibit aggregation and fibril formation of the amyloid-beta peptide (A beta). Human clinical trials using SI to treat Alzheimer disease (AD) patients have shown potential benefits. In light of the growing therapeutic potential of SI, the objective of our study was to gain a more thorough understanding of the mechanism of action. In addition to A beta plagues, a prominent pathological feature of AD is the extensive accumulation of autophagic vacuoles (AVs) suggesting dysfunction in this degradation pathway. Using the TgCRND8 mouse model for AD, we examined SI treatment effects on various components of the autophagic pathway. Autophagy impairment in TgCRND8 mice occurs in the latter stages of the pathway where AV-lysosome fusion and lysosomal degradation take place. SI treatment attenuated this impairment with a decrease in the size and the number of accumulated AVs. We propose that the beneficial effects of SI-A beta, interactions may resolve autophagic deficiencies in the AD brains. Crown Copyright (C) 2012 Published by Elsevier B.V. All rights reserved.
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