Oleuropein regulates neuronal survival and Histone acetylation in Parkinson's disease: cellular and epigenetic insights.
Oleuropein regulates neuronal survival and Histone acetylation in Parkinson's disease: cellular and epigenetic insights.
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Original abstract
The complex physiology of Parkinson's disease (PD) and its limited response to conventional therapies make it a challenging condition to manage. Evidence suggests that both environmental and genetic variables play essential roles in the progression of PD. However, the possible interplay between environment and genetics in PD etiology remains mostly unresolved. Brain-derived neurotrophic factor (BDNF) is a neurotrophin widely distributed and intensively investigated in the mammalian brain. BDNF modulates dopaminergic neurotransmission via neuronal differentiation regulation. BDNF communicates with the Tropomyosin receptor kinase B (TrkB) and activates Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) which can subsequently phosphorylate downstream CREB protein at ser133 residue. Research suggests that numerous health advantages, including significant protections for PD, have been linked to olives, a specific component of the Mediterranean diet. OLE is effective in the treatment of a variety of neurological conditions, including PD. Changes in gene expression patterns induced by aberrant histone acetylation can also aid in the causes of PD. Thus, in the context of neurological diseases, comprehending the epigenetic regulation of the neuronal survival gene is thought to be essential. OLE was first administered intraperitoneally as a pretreatment for seven days. Thereafter, OLE was administered one hour after the rotenone injection for 5 weeks. Herein, we have observed the neuroprotective role of OLE in the cellular signalling cascade associated with neuronal survival through the BDNF/ERK/CREB pathway. Subsequently, we examined the effect of OLE on the enrichment of histone acetylation AcH3K9 in the neuro-survival gene promoter region in PD cases. The data suggest that OLE regulates at both cellular and epigenomic levels by promoting the enrichment of acetylated H3K9 on the neuro-survival gene promoter region in the nigrostriatal region of PD mice.