Olive Oil Polyphenol Oleuropein Shows Promising Neuroprotective Effects in Cellular Model of Parkinson’s Disease

Summary

Parkinson’s dis­ease is char­ac­ter­ized by oxida­tive stress and neu­ronal degen­er­a­tion, with research sug­gest­ing that oleu­ropein, a com­po­nent of olive oil, may have neu­ro­pro­tec­tive effects by reduc­ing oxida­tive stress and mod­u­lat­ing the autophagy process. Studies have shown that oleu­ropein can reduce neu­ron cell death and mito­chon­dr­ial super­ox­ide pro­duc­tion, mak­ing it a poten­tial can­di­date for the devel­op­ment of pre­ven­tive ther­a­pies in neu­rode­gen­er­a­tive dis­eases like Parkinson’s.

Described as the sec­ond most com­mon neu­rode­gen­er­a­tive dis­or­der, Parkinson’s dis­ease (PD) has long been asso­ci­ated with high lev­els of oxida­tive stress. The pri­mary char­ac­ter­is­tic of PD is a pro­gres­sive loss of neu­ro­trans­mit­ter dopamine and neu­ronal degen­er­a­tion lead­ing to the devel­op­ment of motor symp­toms.

Oxidative stress results from an accu­mu­la­tion of reac­tive oxy­gen species (ROS) and evi­dence sug­gests that it con­tributes to the patho­gen­e­sis of PD by affect­ing the mito­chon­dr­ial dys­func­tion, apop­to­sis, inflam­ma­tory response or lyso­so­mal degra­da­tion (autophagy) path­ways.
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In par­tic­u­lar, since the autophagy-lyso­so­mal path­way is known to be the cen­tral cel­lu­lar mech­a­nism for pro­tein aggre­gate degra­da­tion and removal of dam­aged mito­chon­dria, dis­rup­tion of the autophagy-lyso­so­mal path­way by ROS has been impli­cated in the patho­gen­e­sis of PD and of great inter­est as a ther­a­peu­tic tar­get.

The main chal­lenge with the treat­ment of PD is due to the late clin­i­cal pre­sen­ta­tion when neu­ronal loss has already occurred, thus efforts are con­cen­trated on find­ing strate­gies that pro­tect or halt neu­ron loss.

Increasing evi­dence has shown nat­ural polyphe­nols such as cat­e­chins, resver­a­trol and isoflavons exert neu­ro­pro­tec­tive effects by decreas­ing oxida­tive stress, inflam­ma­tion and neu­ron death (apop­to­sis). In par­tic­u­lar, oleu­ropein (OLE), one of the major phe­no­lic com­po­nents of olive oil, has been demon­strated to have a broad spec­trum of ther­a­peu­tic ben­e­fits includ­ing anti-inflam­ma­tory, anti-oxi­dant, anti-can­cer as well as antimi­cro­bial activ­i­ties.

Of inter­est, OLE has been found to reduce apop­to­sis and ROS gen­er­a­tion in pre­clin­i­cal mod­els. Recent find­ings of a study pub­lished in the International Journal of Molecular Science indi­cated treat­ment of neu­ronal PC12 cells with OLE not only low­ered oxida­tive stress lev­els and apop­to­sis but also mod­u­lated the autophagy process.

The researchers ini­tially treated cells with OLE before the addi­tion of a potent Parkinson toxin (6‑OHDA) demon­strat­ing sig­nif­i­cant reduc­tion in neu­ron cell death, and con­cluded that ​“these results endorse OLE as a pro-sur­vival mol­e­cule play­ing a pre­ven­tive pro-sur­vival role in our cel­lu­lar par­a­digm.”

Further data in sup­port of the neu­ro­pro­tec­tive effect of OLE was obtained when the same cel­lu­lar model was treated with OLE before the addi­tion of a pow­er­ful inhibitor of the super­ox­ide dis­mu­tase enzyme (known as DDC), result­ing in a con­sid­er­able reduc­tion in mito­chon­dr­ial super­ox­ide pro­duc­tion.

Next, the researchers assessed bio­marker expres­sion spe­cific to the autophagy process. Their data sug­gested OLE plays a novel role in pre­vent­ing autophagy stim­u­la­tion by affect­ing the expres­sion lev­els of pro­teins involved in the lyso­so­mal path­way.

The authors cau­tioned that while ​“these results sup­port a role for OLE as a mod­u­la­tor of the autophagic flux, autophagy acti­va­tion is also linked to neu­ronal death” and there­fore the exact role and use of OLE in lyso­so­mal degra­da­tion path­way requires fur­ther research before clin­i­cal trans­la­tion as a ther­a­peu­tic tar­get of the autophagy process.

The final take-home mes­sage of the study was that ​“these data solid­ify oleu­ropein as a can­di­date for the devel­op­ment of novel pre­ven­tive ther­a­pies in neu­rode­gen­er­a­tive dis­eases with a facet of oxida­tive stress and/or impair­ment of autophagy, such as in Parkinson’s Disease.”

• International Journal of Molecular Science