Enzyme Plays Key Role in Parkinson’s Disease

Bruce Hammock, Ph.D.
University of California, Berkeley
R01ES002710, P42ES004699

New research by NIEHS grantees and colleagues suggested an enzyme in the brain plays a key role in Parkinson’s disease (PD). Scientists demonstrated that inhibiting the enzyme soluble epoxide hydrolase (sEH) in mice helped curb the inflammation associated with the development and progression of PD.

The researchers exposed mice to methyl-4-phenyl-1, 2, 3, 6 tetrahydropyridine (MPTP), a neurotoxicant that leads to symptoms of PD in animals. They found two approaches that protected against MPTP-induced neurotoxicity in the mouse brain — adding a potent sEH inhibitor, and genetically modifying mice to not produce sEH.

When the researchers examined expression of sEH, they found that it was higher in a specific part of the brain of MPTP-treated mice. Looking in humans, they reported that the enzyme was highly expressed in neurons from the stem cells of a PD patient and from the brains of patients with a disease called dementia of Lewy bodies. This form of dementia, like PD, involves deposits of a protein called alpha-synuclein in multiple regions of the brain.

According to the authors, the research suggested that sEH inhibitors could be potentially useful to reduce or prevent the progression of PD and other related diseases.

Citation: Ren Q, Ma M, Yang J, Nonaka R, Yamaguchi A, Ishikawa KI, Kobayashi K, Murayama S, Hwang SH, Saiki S, Akamatsu W, Hattori N, Hammock BD, Hashimoto K. 2018. Soluble epoxide hydrolase plays a key role in the pathogenesis of Parkinson's disease. Proc Natl Acad Sci U S A 115(25):E5815–E5823.