Gamma-linolenic acid ameliorates Aβ-induced neuroinflammation through NF-κB and MAPK signalling pathways

• Published in: Journal of functional foods 2018-03, Vol.42, p.30-37
• Main Authors: Youn, Kumju, Lee, Seonah, Jun, Mira
• Format: Article
• Language: English
• Subjects: Alzheimer’s disease; Amyloid β; Gamma-linolenic acid; Inflammation; NF-κB
• ISSN: 1756-4646; 2214-9414
• DOI: 10.1016/j.jff.2017.12.065

[Display omitted] •Anti-inflammatory activities and their molecular mechanism of GLA were studied.•GLA inhibited Aβ25–35-induced intracellular ROS and apoptosis.•GLA blocked activation of NF-κB translocation induced by Aβ25–35.•GLA suppressed Aβ25–35-stimulated ERK and JNK phosphorylation. Beta-amyloid (Aβ) are known to form senile plaques causing neuroinflammation, which was accepted as the major pathological mechanism in Alzheimer’s disease (AD). To elucidate the molecular mechanism of gamma-linolenic acid (GLA) on neuroprotective actions in inflammation, the effect of GLA on Aβ25–35-stimulated in PC12 cells was investigated. Pre-treatment of GLA significantly decreased Aβ25–35-mediated cytotoxicity through the reduction of ROS and downregulation of caspase-3, thereby attenuating apoptotic morphological alteration. GLA inhibited the production of proinflammatory cytokines including TNF-α and PGE2, and further blocked NF-κB subunit p65 activation by suppressing IκB-α degradation. Mechanistic studies revealed that the inhibitory effect of GLA was accompanied by reducing expression of ERK1/2 and JNK activity but not by p38 MAPK. In conclusion, given that GLA prevents the Aβ25–35 damage via NF-κB signaling pathway, all of which may provide an exciting view of the potential application of GLA as a future research for AD.