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

Muraleva, Natalia A.; Kozhevnikova, Oyuna S.; Фурсова, А. Ж.; Kolosova, N. G.

doi:10.3390/antiox8060177

Cited by 25 publications

(25 citation statements)

References 65 publications

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“…One of them is believed to be aberrant proteostasis with accumulation of aggregated proteins. It is noteworthy that the therapeutic effect of SkQ1 is associated with a slowdown of Aβ accumulation and significantly decreased activity of mTOR signaling in the retina of OXYS rats [32].…”

Section: Oxys Oxys + Skq1mentioning

confidence: 98%

SkQ1 Suppresses the p38 MAPK Signaling Pathway Involved in Alzheimer’s Disease-Like Pathology in OXYS Rats

2020

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Alzheimer’s disease (AD) is the most common type of dementia and is currently incurable, and mitogen-activated protein kinase (MAPK) p38 is implicated in the pathogenesis of AD. p38 MAPK inhibition is considered a promising strategy against AD, but there are no safe inhibitors capable of penetrating the blood–brain barrier. Earlier, we have shown that mitochondria-targeted antioxidant plastoquinonyl-decyltriphenylphosphonium (SkQ1) at nanomolar concentrations can prevent, slow down, or partially alleviate AD-like pathology in accelerated-senescence OXYS rats. Here we confirmed that dietary supplementation with SkQ1 during active progression of AD-like pathology in OXYS rats (aged 12–18 months) suppresses AD-like pathology progression, and for the first time, we showed that its effects are associated with suppression of p38 MAPK signaling pathway (MAPKsp) activity. Transcriptome analysis, western blotting, and immunofluorescent staining revealed that SkQ1 suppresses p38 MAPKsp activity in the hippocampus at the level of expression of genes involved in the p38 MAPKsp and reduces the phosphorylation of intermediate kinases (p38 MAPK and MK2) and a downstream protein (αB-crystallin). Thus, the anti-AD effects of SkQ1 are associated with improvement in the functioning of relevant signaling pathways and intracellular processes, thus making it a promising therapeutic agent for human AD.

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Section: Oxys Oxys + Skq1mentioning

confidence: 98%

SkQ1 Suppresses the p38 MAPK Signaling Pathway Involved in Alzheimer’s Disease-Like Pathology in OXYS Rats

2020

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“…In clinic, AMD displays the accumulation of Aβ in the drusen beneath the RPE, Aβ-targeted agents and anti-in ammatory therapies are still under evaluation for the treatment of AMD [18][19][20]. Accordingly, it is required to elucidate the mechanisms of AMD is of great importance to understand its pathogenesis and the effective treatments.…”

Section: Discussionmentioning

confidence: 99%

Activated microglia-induced neuroinflammatory cytokines lead to photoreceptor apoptosis in age-related macular degeneration-like mice model

Gao

Shi

et al. 2020

Preprint

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Background: Age-related macular degeneration (AMD) is mainly characterized by progressive deposits of drusen and photoreceptor apoptosis. Due to amyloid β (Aβ) is the main component of drusen, there is a great possibility that Aβ-induced activated microglia leads to inflammation, and plays a critical role in the pathogenesis of AMD. However, the relationship between activated microglia-mediated neuroinflammatory cytokines and photoreceptor apoptosis still remains unclarified.Results: In this study, we demonstrated that subretinal injection of Aβ1-42 induced the microglia activation and increased inflammatory cytokines, gave rise to photoreceptor apoptosis in mice. Our results were verified in vitro by co-culture of Aβ1-42 activated primary microglia and photoreceptor cell line 661W, and we also performed that p38 MAPK signaling pathway was involved in Aβ1-42 induced microglia activation and inflammatory cytokines release.Conclusions: Overall, our findings indicated that activated microglia-mediated neuroinflammatory cytokines contributed to photoreceptor apoptosis under the stimulation of Aβ1-42. Moreover, this study will provide a potential preventive and therapeutic approach for AMD treatment.

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“…In clinic, AMD displays the accumulation of Aβ in the drusen beneath the RPE, Aβ-targeted agents and antiinflammatory therapies are still under evaluation for the treatment of AMD [18][19][20]. Accordingly, it is required to elucidate the mechanisms of AMD is of great importance to understand its pathogenesis and the effective treatments.…”

Section: Discussionmentioning

confidence: 99%

Activated microglia-induced neuroinflammatory cytokines lead to photoreceptor apoptosis in age-related macular degeneration-like mice model

Gao

Shi

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Age-related macular degeneration (AMD) is mainly characterized by progressive deposits of drusen and photoreceptor apoptosis. Due to amyloid β (Aβ) is the main component of drusen, there is a great possibility that Aβ-induced activated microglia leads to inflammation, and plays a critical role in the pathogenesis of AMD. However, the relationship between activated microglia-mediated neuroinflammatory cytokines and photoreceptor apoptosis still remains unclarified. Results In this study, we demonstrated that subretinal injection of Aβ1−42 induced the microglia activation and increased inflammatory cytokines, gave rise to photoreceptor apoptosis in mice. Our results were verified in vitro by co-culture of Aβ1−42 activated primary microglia and photoreceptor cell line 661W, and we also performed that p38 MAPK signaling pathway was involved in Aβ1−42 induced microglia activation and inflammatory cytokines release. Conclusions Overall, our findings indicated that activated microglia-mediated neuroinflammatory cytokines contributed to photoreceptor apoptosis under the stimulation of Aβ1−42. Moreover, this study will provide a potential preventive and therapeutic approach for AMD treatment.

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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

Cited by 25 publications

References 65 publications

SkQ1 Suppresses the p38 MAPK Signaling Pathway Involved in Alzheimer’s Disease-Like Pathology in OXYS Rats

SkQ1 Suppresses the p38 MAPK Signaling Pathway Involved in Alzheimer’s Disease-Like Pathology in OXYS Rats

Activated microglia-induced neuroinflammatory cytokines lead to photoreceptor apoptosis in age-related macular degeneration-like mice model

Activated microglia-induced neuroinflammatory cytokines lead to photoreceptor apoptosis in age-related macular degeneration-like mice model

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