The Moringin/α-CD Pretreatment Induces Neuroprotection in an In Vitro Model of Alzheimer's Disease: A Transcriptomic Study.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and represents the most common form of senile dementia. Autophagy and mitophagy are cellular processes that play a key role in the aggregation of β-amyloid (Aβ) and tau phosphorylation. As a consequence, impairment of these processes leads to the progression of AD. Thus, interest is growing in the search for new natural compounds, such as Moringin (MOR), with neuroprotective, anti-amyloidogenic, antioxidative, and anti-inflammatory properties that could be used for AD prevention. However, MOR appears to be poorly soluble and stable in water. To increase its solubility MOR was conjugated with α-cyclodextrin (MOR/α-CD). In this work, it was evaluated if MOR/α-CD pretreatment was able to exert neuroprotective effects in an AD in vitro model through the evaluation of the transcriptional profile by next-generation sequencing (NGS). To induce the AD model, retinoic acid-differentiated SH-SY5Y cells were exposed to Aβ1-42. The MOR/α-CD pretreatment reduced the expression of the genes which encode proteins involved in senescence, autophagy, and mitophagy processes. Additionally, MOR/α-CD was able to induce neuronal remodeling modulating the axon guidance, principally downregulating the Slit/Robo signaling pathway. Noteworthy, MOR/α-CD, modulating these important pathways, may induce neuronal protection against Aβ1-42 toxicity as demonstrated also by the reduction of cleaved caspase 3. These data indicated that MOR/α-CD could attenuate the progression of the disease and promote neuronal repair.

• Authors: Serena Silvestro, Luigi Chiricosta, Agnese Gugliandolo, Renato Iori, Patrick Rollin, Daniele Perenzoni, Fulvio Mattivi, Placido Bramanti, Emanuela Mazzon
• Journal: Current issues in molecular biology (Curr Issues Mol Biol) Vol. 43 Issue 1 Pg. 197-214 (May 26 2021) ISSN: 1467-3045 [Electronic] Switzerland
• PMID: 34073287 (Publication Type: Journal Article)

Chemical References

• Cyclodextrins
• Isothiocyanates
• Neuroprotective Agents
• moringin

Topics

• Alzheimer Disease (drug therapy, metabolism, pathology, prevention & control)
• Cyclodextrins (chemistry)
• Humans
• Isothiocyanates (chemistry, pharmacology)
• Neuronal Plasticity
• Neuroprotective Agents (pharmacology)
• Transcriptome