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Interplay between Autophagy and the Ubiquitin-Proteasome System and Its Role in the Pathogenesis of Age-Related Macular Degeneration

1
Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland
2
Department of Orthodontics, Medical University of Lodz, 92-216 Lodz, Poland
3
Department of Pediatric Dentistry, Medical University of Lodz, 92-216 Lodz, Poland
4
Department of Ophthalmology, University of Eastern Finland, Kuopio 70211, Finland
5
Department of Ophthalmology, Kuopio University Hospital, 70029 Kuopio, Finland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(1), 210; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20010210
Received: 10 December 2018 / Revised: 21 December 2018 / Accepted: 2 January 2019 / Published: 8 January 2019
(This article belongs to the Special Issue Molecular Biology of Age-Related Macular Degeneration (AMD))
Age-related macular degeneration (AMD) is a complex eye disease with many pathogenesis factors, including defective cellular waste management in retinal pigment epithelium (RPE). Main cellular waste in AMD are: all-trans retinal, drusen and lipofuscin, containing unfolded, damaged and unneeded proteins, which are degraded and recycled in RPE cells by two main machineries—the ubiquitin-proteasome system (UPS) and autophagy. Recent findings show that these systems can act together with a significant role of the EI24 (etoposide-induced protein 2.4 homolog) ubiquitin ligase in their action. On the other hand, E3 ligases are essential in both systems, but E3 is degraded by autophagy. The interplay between UPS and autophagy was targeted in several diseases, including Alzheimer disease. Therefore, cellular waste clearing in AMD should be considered in the context of such interplay rather than either of these systems singly. Aging and oxidative stress, two major AMD risk factors, reduce both UPS and autophagy. In conclusion, molecular mechanisms of UPS and autophagy can be considered as a target in AMD prevention and therapeutic perspective. Further work is needed to identify molecules and effects important for the coordination of action of these two cellular waste management systems. View Full-Text
Keywords: age-related macular degeneration; autophagy; mitophagy; ubiquitin-proteasome system; cellular waste elimination; proteostasis age-related macular degeneration; autophagy; mitophagy; ubiquitin-proteasome system; cellular waste elimination; proteostasis
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MDPI and ACS Style

Blasiak, J.; Pawlowska, E.; Szczepanska, J.; Kaarniranta, K. Interplay between Autophagy and the Ubiquitin-Proteasome System and Its Role in the Pathogenesis of Age-Related Macular Degeneration. Int. J. Mol. Sci. 2019, 20, 210. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20010210

AMA Style

Blasiak J, Pawlowska E, Szczepanska J, Kaarniranta K. Interplay between Autophagy and the Ubiquitin-Proteasome System and Its Role in the Pathogenesis of Age-Related Macular Degeneration. International Journal of Molecular Sciences. 2019; 20(1):210. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20010210

Chicago/Turabian Style

Blasiak, Janusz, Elzbieta Pawlowska, Joanna Szczepanska, and Kai Kaarniranta. 2019. "Interplay between Autophagy and the Ubiquitin-Proteasome System and Its Role in the Pathogenesis of Age-Related Macular Degeneration" International Journal of Molecular Sciences 20, no. 1: 210. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20010210

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