1. NeuroprotectiveEffect of Sulforaphane against MethylglyoxalCytotoxicity.
- Author
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Cristina Angeloni, Marco Malaguti, Benedetta Rizzo, Maria Cristina Barbalace, Daniele Fabbri, and Silvana Hrelia
- Subjects
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NEUROPROTECTIVE agents , *SULFORAPHANE , *PYRUVALDEHYDE , *CELL-mediated cytotoxicity , *ADVANCED glycation end-products , *TREATMENT of neurodegeneration , *THERAPEUTICS - Abstract
Glycation, an endogenous processthat leads to the production ofadvanced glycation end products (AGEs), plays a role in the etiopathogenesisof different neurodegenerative diseases, such as Alzheimer’sdisease (AD). Methylglyoxal is the most potent precursor of AGEs,and high levels of methylglyoxal have been found in the cerebrospinalfluid of AD patients. Methylglyoxal may contribute to AD both inducingextensive protein cross-linking and mediating oxidative stress. Theaim of this study was to investigate the role of sulforaphane, anisothiocyanate found in cruciferous vegetables, in counteracting methylglyoxal-induceddamage in SH-SY5Y neuroblastoma cells. The data demonstrated thatsulforaphane protects cells against glycative damage by inhibitingactivation of the caspase-3 enzyme, reducing the phosphorylation ofMAPK signaling pathways (ERK1/2, JNK, and p38), reducing oxidativestress, and increasing intracellular glutathione levels. For the firsttime, we demonstrate that sulforaphane enhances the methylglyoxaldetoxifying system, increasing the expression and activity of glyoxalase1. Sulforaphane modulated brain-derived neurotrophic factor and itspathway, whose dysregulation is related to AD development. Moreover,sulforaphane was able to revert the reduction of glucose uptake causedby methylglyoxal. In conclusion, sulforaphane demonstrates pleiotropicbehavior thanks to its ability to act on different cellular targets,suggesting a potential role in preventing/counteracting multifactorialneurodegenerative diseases such as Alzheimer’s. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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