oleuropein and Parkinson-Disease

Major pathological features of Parkinson's disease (PD) include increase in oxidative stress leading to the aggregation of α-synuclein, mitochondrial dysfunction and apoptosis of dopaminergic neurons. In addition, downregulation of the expression of neurotrophic factors like-Brain Derived Neurotrophic Factor (BDNF) is also involved in PD progression. There has been a lot of interest in trophic factor-based neuroprotective medicines over the past few decades to treat PD symptoms. Rotenone, an insecticide, inhibits the mitochondrial complex I causing overproduction of ROS, oxidative stress, and aggregation of α-synuclein. It has been shown that BDNF and Tropomyosin receptor kinase B (TrkB) interaction initiates the regulation of neuronal cell development and differentiation by the serine/threonine protein kinases like Akt and GSK-3β. Additionally, Transcription factor CREB (cAMP Response Element-binding protein) also determines the gene expression of BDNF. The homeostasis of these signalling cascades is compromised with the progression of PD. Therefore, maintaining the equilibrium of these signalling cascades will delay the onset of PD. Oleuropein (OLE), a polyphenolic compound present in olive leaves has been documented to cross blood brain barrier and shows potent antioxidative property. In the present study, the dose of 8, 16 and 32 mg/kg body weight (bwt) OLE was taken for dose standardisation. The optimised doses of 16 and 32 mg/kg bwt was found to be neuroprotective in Rotenone induced PD mouse model. OLE improves motor impairment and upregulate CREB regulation along with phosphorylation of Akt and GSK-3β in PD mouse. In addition, OLE also reduces the mitochondrial dysfunction by activation of enzyme complexes and downregulates the proapoptotic markers in Rotenone intoxicated mouse model. Overall, our study suggests that OLE may be used as a therapeutic agent for treatment of PD by regulating BDNF/CREB/Akt signalling pathway.

Topics: alpha-Synuclein; Animals; Brain-Derived Neurotrophic Factor; Dopaminergic Neurons; Glycogen Synthase Kinase 3 beta; Mice; Neuroprotection; Neuroprotective Agents; Parkinson Disease; Proto-Oncogene Proteins c-akt; Rotenone

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Blood Pressure; Diet, Mediterranean; Humans; Hypertension; Iridoid Glucosides; Iridoids; Mice; Olea; Oxidative Stress; Parkinson Disease; Phenylethyl Alcohol; Rats

Parkinson's disease (PD) is a progressive neurodegenerative disorder, primarily affecting dopaminergic neurons in the substantia nigra. There is currently no cure for PD and present medications aim to alleviate clinical symptoms, thus prevention remains the ideal strategy to reduce the prevalence of this disease. The goal of this study was to investigate whether oleuropein (OLE), the major phenolic compound in olive derivatives, may prevent neuronal degeneration in a cellular dopaminergic model of PD, differentiated PC12 cells exposed to the potent parkinsonian toxin 6-hydroxydopamine (6-OHDA). We also investigated OLE's ability to mitigate mitochondrial oxidative stress and modulate the autophagic flux. Our results obtained by measuring cytotoxicity and apoptotic events demonstrate that OLE significantly decreases neuronal death. OLE could also reduce mitochondrial production of reactive oxygen species resulting from blocking superoxide dismutase activity. Moreover, quantification of autophagic and acidic vesicles in the cytoplasm alongside expression of specific autophagic markers uncovered a regulatory role for OLE against autophagic flux impairment induced by bafilomycin A1. Altogether, our results define OLE as a neuroprotective, anti-oxidative and autophagy-regulating molecule, in a neuronal dopaminergic cellular model.

Topics: Animals; Autophagy; Cell Death; Iridoid Glucosides; Iridoids; Mitochondria; Nerve Degeneration; Oxidative Stress; Oxidopamine; Parkinson Disease; PC12 Cells; Rats; Reactive Oxygen Species; Superoxides