Therapeutic potential of PGC-1 alpha in age-related macular degeneration (AMD) - the involvement of mitochondrial quality control, autophagy, and antioxidant response

Introduction: Age-related macular degeneration (AMD) is the leading, cause of sight loss in the elderly in the Western world. Most patients remain still without any treatment options. The targeting of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha), a transcription co-factor, is a putative therapy against AMD. Areas covered: The characteristics of AMD and their possible connection with PGC-1 alpha as well as the transcriptional and post-transcriptional control of PGC-1 alpha are discussed. The PGC-1 alpha-driven control of mitochondrial functions, and its involvement in autophagy and antioxidant responses are also examined. Therapeutic possibilities via drugs and epigenetic approaches to enhance PGC-1 alpha expression are discussed. Authors conducted a search of literature mainly from the recent decade from the PubMed database. Expert opinion: Therapy options in AMD could include PGC-1 alpha activation or stabilization. This could be achieved by a direct elevation of PGC-1 alpha activity, a stabilization or modification of its upstream activators and inhibitors by chemical compounds, like 5-Aminoimidazole-4-carboxamide riboside, metformin, and resveratrol. Furthermore, manipulations with epigenetic modifiers of PGC-1 alpha expression, including miRNAs, e.g. miR-204, are considered. A therapy aimed at PGC-1 alpha up-regulation may be possible in other disorders besides AMD, if they are associated with disturbances in the mitochondria-antioxidant response-autophagy axis.