MODULATING PROTEOSTASIS AND ENERGY METABOLISM: ESSENTIAL OIL-BASED STRATEGIES IN NEURODEGENERATION

Neurodegenerative diseases such as Parkinson’s disease (PD) are characterized by progressive neuronal loss, driven by multifactorial mechanisms including oxidative stress, mitochondrial dysfunction, and impaired protein homeostasis. In the search for safer, multi-targeted therapeutic approaches, essential oils (EOs) have emerged as promising neuroprotective agents due to their complex phytochemical composition and bioactivity.
In this study, we investigated the neuroprotective effects of Eucalyptus citriodora essential oil (ECEO) using a 6-hydroxydopamine (6-OHDA)-induced PD-like in vitro model in N2a neuroblastoma cells and SH-SY5Y. Our results demonstrated that ECEO, at non-toxic concentrations, significantly preserved cell viability and membrane integrity, reduced reactive oxygen species (ROS) and nitric oxide (NO) production, and mitigated 6-OHDA-induced cytotoxicity. In SH-SY5Y cells, pretreatment with ECEO reduced significantly IL-6 expression and restored BDNF expression. these indicating a potential anti-inflammatory effect and activation of neuronal survival mechanisms, possibly via Nrf2 signaling pathways.
Through 2D gel electrophoresis and MALDI-TOF-TOF mass spectrometry in N2a cells, we identified a set of differentially expressed proteins involved in critical pathways such as proteostasis (26S proteasome, VCP), glycolysis, and mitochondrial complex I function. Functional enrichment analysis further highlighted the modulation of NADH metabolism and protein degradation pathways as key mechanisms underlying ECEO’s neuroprotective effects.
These findings support the potential of ECEO as a multi-target neuroprotective agent and provide a proteomic foundation for its future application in neurodegenerative disease prevention or adjunct therapy. This work also illustrates the value of integrating natural compounds and systems-level proteomic approaches to uncover novel therapeutic strategies.