ROLE OF EDCs IN NEURODEGENERATION AND IT’S PROTECTION BY SOME NEUROPROTECTIVE AGENTS

Abstract

Neurodegeneration, the most concerning global disorder of present time, involves the irreversible egeneration of the neurons, and manifested as age-related diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD). The typical features of these diseases include the generation and aggregation of altered protein which onsets during middle or later ages of human lifespan as an inherited or sporadic disorder. These neurodegenerative factors trigger neuron death by causing structural and functional degeneration. AD is becoming more prevalent in the aging population worldwide. It has been estimated that AD will affect around 16 million people in the USA and around 100 million people worldwide by the end of 2050. The neurological system is harmed by chemical exposure. Endocrine-disrupting chemicals (EDCs) are categorized as one such chemicals with negative impact on the brain. EDCs-mediated impairment is caused by the entangled state of the endocrine and neurological systems. The current thesis entitled “Role of EDCs in Neurodegeneration & it’s protection by some Neuroprotective Agents” examines the effects of one of these EDCs, Triclosan (TCS), in neuroinflammation and potential therapeutic approach using in vitro and in vivo model. This study proposes that TCS promotes TNF-α mediated neuroinflammation in Neuro-2a cells, which leads to RIPK1, RIPK3, and MLKL-associated necroptosis. TCS increases tau protein pathogenesis in Neuro-2a cells, which alludes to the development of tau-associated neurodegeneration. TCS downregulates the expression of tyrosine hydroxylate (TH) and dopamine transporter (DAT) in dopaminergic neurons, which may cause impairment of motor neuron. Wheatgrass is known for its antioxidant properties. Our in vitro and in vivo studies propose the neuroprotective properties of wheatgrass against, both, TCS and scopolamineinduced inflammation. Wheatgrass suppresses the production of TCS-induced inflammatory proteins. Wheatgrass, and its metabolic active compound apigenin, alleviate the TCS induced oxidative stress, and lowers the necroptotic markers RIPK3, MLKL and p-MLKL trimeric aggregates via Akt/ERK-BDNF neurotropic factor pathway. Scopolamine causes loss of memory, termed as amnesia, in mice. The study of hippocampal region of mice brain confirms that this impact is mediated through TNF-α-induced oxidative stress and tau protein aggregation. Wheatgrass enhances the production of neuroprotective markers while lowering the tau protein aggregation in the hippocampal region of scopolamine induced amnesic mice. Collectively, this scientific investigation evident the neurodegenerative properties of TCS and neuroprotective role of wheatgrass.