EGCG-like non-competitive inhibitor of DYRK1A rescues cognitive defect in a down syndrome model

Delabar, Jean M.; Gomes, Marco Antônio G.B.; Fructuoso, Marta; Sarrazin, Nadège; George, Nicolas; Fleary-Roberts, Nadia; Sun, Hua; Bui, Linh Chi; Rodrigues-Lima, Fernando; Janel, Nathalie; Dairou, Julien; Maria, Edmilson J.; Dodd, Robert H.; Cariou, Kevin; Potier, Marie-Claude

doi:10.1016/j.ejmech.2023.116098

Cited by 5 publications

(2 citation statements)

References 53 publications

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“…Adult Dp(16)1Yey mice and WT controls have similar weight curves, and so we chose to use a working memory test (the Y-maze); the SPA rate was lower in Dp(16)1Yey mice [ 22 , 37 ]. Similarly, Dp(16)1Yey mice have normal levels of locomotor activity but spent more time in the center [ 38 , 39 ]. sPIF treatment partially restored the level of cognitive performances and had a long-term effect.…”

Section: Discussionmentioning

confidence: 99%

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Prenatal treatment with preimplantation factor improves early postnatal neurogenesis and cognitive impairments in a mouse model of Down syndrome

Moreau,

Dard,

Madani

et al. 2024

Cell. Mol. Life Sci.

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Down syndrome (DS) is a genetic disease characterized by a supernumerary chromosome 21. Intellectual deficiency (ID) is one of the most prominent features of DS. Central nervous system defects lead to learning disabilities, motor and language delays, and memory impairments. At present, a prenatal treatment for the ID in DS is lacking. Subcutaneous administration of synthetic preimplantation factor (sPIF, a peptide with a range of biological functions) in a model of severe brain damage has shown neuroprotective and anti-inflammatory properties by directly targeting neurons and microglia. Here, we evaluated the effect of PIF administration during gestation and until weaning on Dp(16)1Yey mice (a mouse model of DS). Possible effects at the juvenile stage were assessed using behavioral tests and molecular and histological analyses of the brain. To test the influence of perinatal sPIF treatment at the adult stage, hippocampus-dependent memory was evaluated on postnatal day 90. Dp(16)1Yey pups showed significant behavioral impairment, with impaired neurogenesis, microglial cell activation and a low microglial cell count, and the deregulated expression of genes linked to neuroinflammation and cell cycle regulation. Treatment with sPIF restored early postnatal hippocampal neurogenesis, with beneficial effects on astrocytes, microglia, inflammation, and cell cycle markers. Moreover, treatment with sPIF restored the level of DYRK1A, a protein that is involved in cognitive impairments in DS. In line with the beneficial effects on neurogenesis, perinatal treatment with sPIF was associated with an improvement in working memory in adult Dp(16)1Yey mice. Perinatal treatment with sPIF might be an option for mitigating cognitive impairments in people with DS.

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Section: Discussionmentioning

confidence: 99%

“…Therapeutic strategies based on reducing the activity of DYRK1A (e.g. leucettine L41 and a green tea extract enriched in epigallocatechin gallate) have shown beneficial effects in DS models, including Dp(16)1Yey mice [ 38 , 56 , 57 ]. Importantly, sPIF treatment influences the level of DYRK1A protein.…”

Section: Discussionmentioning

confidence: 99%

Prenatal treatment with preimplantation factor improves early postnatal neurogenesis and cognitive impairments in a mouse model of Down syndrome

Moreau,

Dard,

Madani

et al. 2024

Cell. Mol. Life Sci.

Self Cite

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Alzheimer’s drugs, APPlication for Down syndrome?

Sokol,

Lahiri

2024

Ageing Research Reviews

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Epigallocatechin-3-gallate therapeutic potential in human diseases: molecular mechanisms and clinical studies

Alam,

Gulzar,

Akhtar

et al. 2024

Mol Biomed

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Green tea has garnered increasing attention across age groups due to its numerous health benefits, largely attributed to Epigallocatechin 3-gallate (EGCG), its key polyphenol. EGCG exhibits a wide spectrum of biological activities, including antioxidant, anti-inflammatory, antibacterial, anticancer, and neuroprotective properties, as well as benefits for cardiovascular and oral health. This review provides a comprehensive overview of recent findings on the therapeutic potential of EGCG in various human diseases. Neuroprotective effects of EGCG include safeguarding neurons from damage and enhancing cognitive function, primarily through its antioxidant capacity to reduce reactive oxygen species (ROS) generated during physiological stress. Additionally, EGCG modulates key signaling pathways such as JAK/STAT, Delta-Notch, and TNF, all of which play critical roles in neuronal survival, growth, and function. Furthermore, EGCG is involved in regulating apoptosis and cell cycle progression, making it a promising candidate for the treatment of metabolic diseases, including cancer and diabetes. Despite its promising therapeutic potential, further clinical trials are essential to validate the efficacy and safety of EGCG and to optimize its delivery to target tissues. While many reviews have addressed the anticancer properties of EGCG, this review focuses on the molecular mechanisms and signaling pathways by which EGCG used in specific human diseases, particularly cancer, neurodegenerative and metabolic diseases. It serves as a valuable resource for researchers, clinicians, and healthcare professionals, revealing the potential of EGCG in managing neurodegenerative disorders, cancer, and metabolic diseases and highlighting its broader therapeutic values.

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EGCG-like non-competitive inhibitor of DYRK1A rescues cognitive defect in a down syndrome model

Cited by 5 publications

References 53 publications

Prenatal treatment with preimplantation factor improves early postnatal neurogenesis and cognitive impairments in a mouse model of Down syndrome

Prenatal treatment with preimplantation factor improves early postnatal neurogenesis and cognitive impairments in a mouse model of Down syndrome

Alzheimer’s drugs, APPlication for Down syndrome?

Epigallocatechin-3-gallate therapeutic potential in human diseases: molecular mechanisms and clinical studies

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