The Lindane is an organochlorinated pesticides (OCPs) which belongs to the chlorinated hydrocarbon family, a group of organic compounds, known as "persistent organic pollutants" (POPs). This compounds are resistant to degradation or biodegradation and they can be bioaccumulated into adipose tissue because of their lipotropic properties and great stability. Recently, several authors have pointed out the close relationship between pesticides exposure and neurodegenerative disorders, such as Parkinson's disease. To date, the biochemical and molecular pathways involved in ß-HCH health damages are not yet fully understood. Given the interest in the understanding the role of OCP exposure in the neurodegenerative processes, such as Alzheimer's, Parkinson's and Amyotrophic Lateral Sclerosis diseases, and the increasing evidences on the pivotal role of the epigenetic mechanisms in tracking the course and development of the diseases, the aim of this project is to investigate the effects of the ß-isomer of hexachlorocyclohexane (ß-HCH), a lindane synthesis byproduct, at the molecular levels on neuronal cells. Our preliminary studies on inflammation response induced by ß-HCH in microglia cells highlighted promising results on NF-kB pathways. Considering that NF-kB is associated to histone deacetylases nuclear-cytosol translocation, it is noteworthy to identify and investigate HDAC-protein complex and the contribute of ß-HCH-induced histone post-translational modification (PTM) in neuronal cells by using multi-omics technologies. Moreover, since many studies have revealed neuroprotective effects exerted by polyphenols, this research is also aimed to characterize new bioactive compounds from Phyllanthus orbicularis Kunth, an endemic evergreen plant of Cuba, which is widely used by traditional medical practitioners for the treatment of different types of diseases. Experiments with this plant extract will be carried out in order to explore its ability to counteract ß-HCH toxicity.
This research will shed light on the ability of ß-HCH to induce inflammatory gene expression thought epigenetic modulation. This work will extend our knowledge on molecular processes underlying ß-HCH neuronal toxicity. Our research is focused on the altered epigenetic profile that contribute to the modulation of neurotoxic gene expression. In particular, the ß-HCH impact on the neuronal epigenome could be essential to understand the pathophysiological molecular mechanisms related to the exposure of environmental toxic chemicals. Therefore, we consider this project innovative because it will offer a new paradigm for understanding how epigenetic modifications mediate the Organochlorine pesticide effects on human health. For this reason, clarifying the effect of ß-HCH on the transcription regulation of inflammatory genes, we provide a new potential therapeutic approach for ß-HCH-related to brain diseases. Since dietary polyphenol-targeted epigenetics might be an attractive approach for disease prevention and intervention, the utilization of Phyllantus extract and Fideloside might represent an alternative therapeutic strategy to counteract neurotoxicity induced by ß-HCH exposure.