Bioactivated Glucoraphanin Improves Cell Survival, Upregulating Phospho-AKT, and Modulates Genes Involved in DNA...

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Alzheimer's disease (AD) lacks a definitive cure, prompting research into natural compounds for neuroprotection.
• Sulforaphane (SFN), derived from glucoraphanin (GRA) in cruciferous vegetables, is known to mitigate neuronal dysfunction, apoptosis, and oxidative stress.
• SFN's potential neuroprotective mechanisms warrant investigation, particularly its effects on neurons exposed to amyloid-beta (Aβ).

Purpose of the Study:

• To investigate the molecular effects of SFN pre-treatment on differentiated SH-SY5Y neurons exposed to Aβ.
• To assess SFN's impact on cell viability and gene expression profiles following Aβ exposure.
• To elucidate the biological pathways modulated by SFN in the context of Aβ-induced neuronal damage.

Main Methods:

• Cell viability was assessed using the Thiazolyl Blue Tetrazolium Bromide (MTT) assay.
• Transcriptomic profiles were analyzed via next-generation sequencing (NGS).
• Network analysis and Western blot assays were employed to identify and validate affected biological processes and molecular changes.

Main Results:

• SFN pre-treatment effectively counteracted the loss of cell viability induced by Aβ.
• Network-transcriptomic analysis revealed SFN-mediated upregulation of DNA repair genes, including ABRAXAS1, BRCA1, BRCA2, CDKN1A, FANCA, FANCD2, FANCE, NBN, and XPC.
• SFN increased AKT phosphorylation, a key signaling pathway involved in DNA repair and cell survival.

Conclusions:

• SFN demonstrates neuroprotective properties by enhancing cell survival and potentially restoring DNA damage caused by Aβ exposure.
• These findings suggest SFN's potential utility as a natural compound for Alzheimer's disease prevention.
• SFN modulates key molecular pathways, including DNA repair and cell survival signaling, in response to Aβ insult.