ArticleACS chemical neuroscience2013
Retinoic acid-elicited RARα/RXRα signaling attenuates Aβ production by directly inhibiting γ-secretase-mediated cleavage of amyloid precursor protein.
Article in ACS chemical neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Natural Compounds for Alzheimer's Disease Therapy: A Systematic Review of Preclinical and Clinical Studies.International journal of molecular sciences · 2019Pooled it
- Bioinorganic Chemistry of Micronutrients Related to Alzheimer's and Parkinson's Diseases.Molecules (Basel, Switzerland) · 2023Review
- Thwarting Alzheimer's Disease through Healthy Lifestyle Habits: Hope for the Future.Neurology international · 2023Review
- Amylin and Secretases in the Pathology and Treatment of Alzheimer's Disease.Biomolecules · 2022Review
- Revisiting APP secretases: an overview on the holistic effects of retinoic acid receptor stimulation in APP processing.Cellular and molecular life sciences : CMLS · 2022Review
- Role of Retinoid X Receptors (RXRs) and dietary vitamin A in Alzheimer's disease: Evidence from clinicopathological and preclinical studies.Neurobiology of disease · 2021Article
- Reduction BACE1 expression via suppressing NF-κB mediated signaling by Tamibarotene in a mouse model of Alzheimer's disease.IBRO neuroscience reports · 2021Article
- Neuroprotection against Amyloid-Neural plasticity · 2020Article
- The protective variant rs7173049 at LOXL1 locus impacts on retinoic acid signaling pathway in pseudoexfoliation syndrome.Human molecular genetics · 2019Article
- Long-term in vitro culture and preliminary establishment of chicken primordial germ cell lines.PloS one · 2018Article
- Molecular Anti-inflammatory Mechanisms of Retinoids and Carotenoids in Alzheimer's Disease: a Review of Current Evidence.Journal of molecular neuroscience : MN · 2017Review
- The Vitamin A Derivative All-Trans Retinoic Acid Repairs Amyloid-β-Induced Double-Strand Breaks in Neural Cells and in the Murine Neocortex.Neural plasticity · 2016Article
- Identification of potential short-chain fatty acid biomarkers in Alzheimer's disease through bioinformatics analysis.Journal of Alzheimer's disease reportsArticle
Corrections and comments
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Authors and funding
6 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Retinoic acid (RA)-elicited signaling has been shown to play critical roles in development, organogenesis, and the immune response. RA regulates expression of Alzheimer's disease (AD)-related genes and attenuates amyloid pathology in a transgenic mouse model. In this study, we investigated whether RA can suppress the production of amyloid-β (Aβ) through direct inhibition of γ-secretase activity. We report that RA treatment of cells results in significant inhibition of γ-secretase-mediated processing of the amyloid precursor protein C-terminal fragment APP-C99, compared with DMSO-treated controls. RA-elicited signaling was found to significantly increase accumulation of APP-C99 and decrease production of secreted Aβ40. In addition, RA-induced inhibition of γ-secretase activity was found to be mediated through significant activation of extracellular signal-regulated kinases (ERK1/2). Treatment of cells with the specific ERK inhibitor PD98059 completely abolished RA-mediated inhibition of γ-secretase. Consistent with these findings, RA was observed to inhibit secretase-mediated proteolysis of full-length APP. Finally, we have established that RA inhibits γ-secretase through nuclear retinoic acid receptor-α (RARα) and retinoid X receptor-α (RXRα). Our findings provide a new mechanistic explanation for the neuroprotective role of RA in AD pathology and add to the previous data showing the importance of RA signaling as a target for AD therapy.
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