5'-Adenosine monophosphate-activated protein kinase--mammalian target of rapamycin axis as therapeutic target for age-related macular degeneration.
Age-related macular degeneration (AMD) is the most common reason for blindness in developed countries. AMD essentially involves chronic oxidative stress, increased accumulation of lipofuscin in retinal pigment epithelial (RPE) cells, and extracellular drusen formation, as well as presence of chronic inflammation in the retina. The capacity to prevent the accumulation of cellular cytotoxic protein aggregates is decreased in senescent cells, which may evoke lipofuscin accumulation into lysosomes in postmitotic RPE cells. The formation of lipofuscin, in turn, decreases the lysosomal enzyme activity and impairs the autophagic clearance of damaged proteins destined for cellular removal. 5'-Adenosine monophosphate-activated protein kinase (AMPK) is a well-known inhibitor of mammalian target of rapamycin (mTOR) that subsequently evokes induction of autophagy. This review examines the novel potential therapeutic targets on the AMPK-mTOR axis and the ways in which autophagy clearance can suppress or prevent RPE degeneration and development of AMD.
Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O.Box 1627, FI-70211 Kuopio, Finland. Juha.Hyttinen@uef.fi
Juha M T
JM
Hyttinen
Goran
G
Petrovski
Antero
A
Salminen
Kai
K
Kaarniranta
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D006801:Humans; D007249:Inflammation; D008062:Lipofuscin / Q000737:chemistry; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal / Q000379:methods; D008954:Models, Biological; D018384:Oxidative Stress; D000077185:Resveratrol; D012160:Retina / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
D008062:Lipofuscin; D013267:Stilbenes; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D000077185:Resveratrol