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. 2024 Jun;32(3):2061-2073.
doi: 10.1007/s10787-024-01466-3. Epub 2024 Apr 2.

Autophagy and exosomes; inter-connected maestros in Alzheimer's disease

Hanaa B Atya  1 , Nadia Mohamed Sharaf  2 , Ragwa Mansour Abdelghany  2 , Sara Nageeb El-Helaly  3 , Heba Taha  4
Affiliations

Autophagy and exosomes; inter-connected maestros in Alzheimer's disease

Hanaa B Atya et al. Inflammopharmacology. 2024 Jun.

Abstract

Autophagy is a crucial process involved in the degradation and recycling of cytoplasmic components which are transported to the lysosomal compartment by autophagosomes. Exosomes are an important means of communication and signaling in both normal and diseased states, and they have a significant role in the transmission and propagation of proteins, especially proteins implicated in neurodegenerative disorders. Autophagy may affect exosomal processing, but whether autophagy controls the release of aggregated β-amyloid and tau proteins in exosomes of Alzheimer disease (AD) is unclear. Therefore, our study aimed to investigate how modulating autophagy affects the exosomal release of these proteins in animal models of AD. Isolated exosomes from brain tissues of 48 male albino mice were divided into four groups (Negative control, LPS, rapamycin (RAPA), and chloroquine (CQ). LC3 I and LC3 II as well as Aβ and Tau proteins levels were determined. All mice undergone Neuro-behavioral tests (Morris Water maze test, Y-maze test, and Novel Object Recognition). Both LPS and CQ groups showed reduced expression levels of LC3 II and LC3 II/LC3 I ratio. In contrast, RAPA group showed a significant increase in both LC3-II expression and LC3-II/LC3-I ratio. The levels of both Aβ & Tau in exosomes of CQ & LPS groups were higher. While RAPA group showed a significant diminished levels of tau & Aβ proteins. In conclusion, our findings suggest that autophagy alterations in AD can influence the release of Aβ and tau proteins through exosomes, which may impact the spread of misfolded proteins in AD. These results highlight a potential innovative therapeutic approach for combating AD.

Keywords: Alzheimer disease (AD); Autophagy; Exosomes.

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Conflict of interest statement

The authors declare that they have no financial or non-financial competing interests that are directly or indirectly related to this work.

Figures

Fig. 1
Fig. 1
Mean Escape Latency in studied groups
Fig. 2
Fig. 2
Day 4 Mean Escape Latency in studied groups. The values were expressed as mean ± SD. using the ANOVA test followed by the Tukey multiple comparison test
Fig. 3
Fig. 3
Probe test in studied groups. The values were expressed as mean ± SD. using the ANOVA test followed by the Tukey multiple comparison test. a: significant from healthy control (negative control), b: significant from LPS group, c: significant from rapamycin group, and d: significant from chloroquine group
Fig. 4
Fig. 4
Spatial memory in studied groups. The values were expressed as mean ± SD. using the ANOVA test followed by the Tukey multiple comparison test. a: significant from healthy control (negative control), b: significant from LPS group, c: significant from rapamycin group, and d: significant from chloroquine group
Fig. 5
Fig. 5
Novelty testing in studied groups. The values were expressed as mean ± SD. using the ANOVA test followed by the Tukey multiple comparison test. a: significant from healthy control (negative control), b: significant from LPS group, c: significant from rapamycin group, and d: significant from chloroquine group
Fig. 6
Fig. 6
Size distribution report by Zetasizer
Fig. 7
Fig. 7
Characterization of exosomes isolated from the brain of Alzheimer’s mice. Immunoblot analysis of exosome preparation is positive for exosome markers HSC70, and CD9 and negative for mitochondrial marker Bcl2, Golgi marker GM130, and nuclear marker nucleoporin p62
Fig. 8
Fig. 8
Western blot analysis of LC3 I & LC3 II, and β-actin was used as loading control
Fig. 9
Fig. 9
Expression level of LC3 II in studied groups. The values were expressed as mean ± SD. using the ANOVA test followed by the Tukey multiple comparison test. a: significant from healthy control (negative control), b: significant from LPS group, c: significant from rapamycin group, and d: significant from chloroquine group
Fig. 10
Fig. 10
LC3 II / LC3 I Ratio in studied groups. The values were expressed as mean ± SD. using the ANOVA test followed by the Tukey multiple comparison test. a: significant from healthy control (negative control), b: significant from LPS group, c: significant from rapamycin group, and d: significant from chloroquine group
Fig. 11
Fig. 11
Level of Amyloid- β in exosomes of studied groups. The values were expressed as mean ± SD. using the ANOVA test followed by the Tukey multiple comparison test. a: significant from healthy control (negative control), b: significant from LPS group, c: significant from rapamycin group, and d: significant from chloroquine group
Fig. 12
Fig. 12
Level of Tau proteins in exosomes of studied groups. The values were expressed as mean ± SD. using the ANOVA test followed by the Tukey multiple comparison test. a: significant from healthy control (negative control), b: significant from LPS group, c: significant from the rapamycin group
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