| Abstract No.: | C-C3090 |
| Country: | Canada |
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| Title: | NANO-CHAPERONES IN ALZHEIMER’S DISEASE |
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| Authors/Affiliations: | 1 Sebastien Boridy*; 1 Maik Behrendt; 1 Dusica Maysinger;
1 McGill University, Montreal, QC, Canada
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| Content: | Objectives. AD has been proposed to be a protein folding disorder and chaperones have been implicated in the pathogenesis of this disease. In the present study, we addressed two questions; (i) how can the regulation of endogenous chaperone molecules in the cortex and hippocampus of hormonally imbalanced old and young mice, with or without landmarks of AD, exert their protective action, and (ii) can novel artificial nano-chaperones promote self-repair or delay AD pathology?
Methods. Sub-cellular distribution of several heat shock proteins (HSP25, HSP60 and HSP70) in enriched organelle preparations isolated from cortices and hippocampi of young and aged mice, with or without hormone imbalance, was assessed by western blotting and immunocytochemistry. Specific antibodies raised against individual HSPs were used. Co-localization of HSPs with organelle-specific dyes and 3D-reconstructions were achieved by employing software developed for this purpose.
Results from these studies show that there are/is, (i) extensive abnormalities in the sub-cellular distributions of several HSPs in the hippocampi and cortices of hormone-imbalanced, aged mice; (ii) significant neuronal degeneration and astroglial activation in hormonally-imbalanced hippocampi; (iii) a discernable difference in the spatio-temporal response of Hsp60 to acute oestradiol treatment, relative to the control and aromatase inhibited cells; and (iv) prevention of amyloid-beta (Aβ42) fibrillation by artificial nano-chaperones, which could provide a new means of nano-delivery to the CNS structures.
Conclusions: This study provides evidence for a novel mechanism of chaperone/oestrogen-mediated neuroprotection, as well as evidence for the therapeutic potential of certain types of nano-particles, which can delay and reduce the severity of neurodegenerative changes in AD. |
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