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Phcog Rev. · Lens · Soluble Epoxide Hydrolase (sEH): A Novel Therapeutic Target in Mitigating the Symptoms of Parkinson’s Disease

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Review · Volume 20, Issue 40 · pp. 154-169

Soluble Epoxide Hydrolase (sEH): A Novel Therapeutic Target in Mitigating the Symptoms of Parkinson’s Disease

Richa Mehta1, Salini Nair2, Sahyadri Manjunath2, Santhepete Nanjundaiah Manjula2, Gokul Ramesh2, Sathish Kumar Gunasekaran2, Mamatha Gavisiddaiah2, Prashant Yuvaraj Mali2

  1. 1Department of Pharmacology, Jagadguru Sri Shivarathreeswara College of Pharmacy, Jagadguru Sri Shivarathreeswara Academy of Higher Education and Research (Deemed to be University), Mysuru, Karnataka, INDIA.
  2. 2Department of Pharmacology and Pharmacy Practice, Yashwantrao Bhonsale College of Pharmacy (Affiliated to University of Mumbai), Sawantwadi, Sindhudurg, Mumbai, Maharashtra, INDIA.

Abstract

Parkinson's Disease (PD) is a progressive neurodegenerative disease characterized by the degeneration of dopaminergic neurons in the substantia nigra, which results in motor control problems. One of the main pathological aspects is the presence of alpha-synuclein aggregates, which are called Lewy bodies. Neuroinflammation is at the centre of PD progression and the contribution of activated microglia, lymphocyte invasion, and increased pro-inflammatory cytokines to neuronal damage. Epoxyeicosatrienoic Acids (EETs), the products of arachidonic acid metabolised through cytochrome P450 epoxygenase, have anti-inflammatory and neuroprotective effects. Specifically, NF-kB activation is inhibited, and BDNF-mediated neuronal survival and neurite outgrowth are enhanced by 11,12-EET. However, EETs are rapidly degraded into less active diols (DHETs) by soluble Epoxide Hydrolase (sEH). sEH inhibition prevents the breakdown of EET, thus elevating their levels and therapeutic potential. The sEH is an attractive approach to inhibiting neuroinflammation and safeguarding dopaminergic neurons in PD.

Keywords: Arachidonic acid; Cytochrome P450; Epoxyeicosatrienoic Acids; Parkinson's disease; Soluble Epoxide Hydrolase.

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