Suppression of AMD-Like Pathology by Mitochondria-Targeted Antioxidant SkQ1 Is Associated with a Decrease in the Accumulation of Amyloid β and in mTOR Activity.

Natalia A Muraleva,Anzhela Z Fursova,Nataliya G Kolosova,Oyuna S Kozhevnikova

doi:10.3390/antiox8060177

Natalia A Muraleva, Anzhela Z Fursova + Show 2 more

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https://doi.org/10.3390/antiox8060177

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Abstract

Age-related macular degeneration (AMD) is a major cause of irreversible visual impairment and blindness in developed countries, and the molecular pathogenesis of AMD is poorly understood. Recent studies strongly indicate that amyloid β (Aβ) accumulation —found in the brain and a defining feature of Alzheimer’s disease—also forms in the retina in both Alzheimer’s disease and AMD. The reason why highly neurotoxic proteins of consistently aggregate in the aging retina, and to what extent they contribute to AMD, remains to be fully addressed. Nonetheless, the hypothesis that Aβ is a therapeutic target in AMD is debated. Here, we showed that long-term treatment with SkQ1 (250 nmol/[kg body weight] daily from the age of 1.5 to 22 months) suppressed the development of AMD-like pathology in senescence-accelerated OXYS rats by reducing the level of Aβ and suppressing the activity of mTOR in the retina. Inhibition of mTOR signaling activity, which plays key roles in aging and age-related diseases, can be considered a new mechanism of the prophylactic effect of SkQ1. It seems probable that dietary supplementation with mitochondria-targeted antioxidant SkQ1 can be a good prevention strategy to maintain eye health and possibly a treatment of AMD.

Highlights

Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment and blindness in industrialized countries
Recent studies strongly indicate that amyloid β (Aβ), found in the brain and a defining feature of Alzheimer’s disease (AD), forms in the retina in both AD and AMD [35,36]
The reason why proteins of this highly neurotoxic family consistently aggregate in the aging retina, and to what extent they contribute to AMD, remains to be fully addressed [25]

Summary

Introduction

Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment and blindness in industrialized countries. The introduction of anti-angiogenesis therapy has helped to prevent blindness and restore vision in wet AMD, there remains no effective treatment for the majority of patients with dry or nonexudative AMD [1]. The pathogenesis of this complex degenerative disease includes both genetic and epigenetic risk factors but is not completely clear. Reactive oxygen species (ROS) are produced mainly in mitochondria, whose dysfunction, in combination with defective proteostasis, is a hallmark of age-related degenerative diseases including AMD and Alzheimer’s disease (AD) [3]. The research to date suggests that antioxidant supplements (at least those studied) do not prevent and certainly do Antioxidants 2019, 8, 177; doi:10.3390/antiox8060177 www.mdpi.com/journal/antioxidants

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