Author(s)

Kazuki Ohuchi¹, Kazuhiro Tsuruma¹, Masamitsu Shimazawa¹, Junji Nakamura², Hideaki Hara^1*

¹Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
²Asahi Kasei Pharma Corporation, Tokyo, Japan.

The expression of cytosolic phospholipase A2 (cPLA2) expression is up-regulated in animal model of ALS and in patients with familial amyotrophic lateral sclerosis (fALS). Inhibition of cyclooxygenase 2 (COX2), which is a downstream enzyme of cPLA2, ameliorates the impairment of motor function in the ALS model mice. Therefore, the arachidonic acid cascade, including the cPLA2-COX2 pathway, is an important therapeutic target of ALS. The current study was designed to investigate the potential of AK106-001616, an inhibitor of cPLA2, in protection of motor neuron cell death induced by mutant superoxide dismutase (SOD1^G93A). AK106-001616 (1 - 10 μM) protected NSC34 cells (mouse motor neuron like cells) against SOD1^G93A-induced motor neuron cell death. Furthermore, aspirin, an inhibitor of COX1/2, reduced the SOD1^G93A-induced motor neuron cell death at a concentration that inhibited COX2. Celecoxib, a selective COX2 inhibitor, also reduced the SOD1^G93A-induced motor neuron cell death. These results suggest that the arachidonic acid cascade is important for SOD1^G93A-induced motor neuron cell death and AK106-001616 has a potent neuroprotective effect against it. AK106-001616 may be a useful therapeutic agent against SOD1^G93A-induced ALS.

AK106-001616, Amyotrophic Lateral Sclerosis, cPLA2, NSC34, SOD1^G93A

Ohuchi, K. , Tsuruma, K. , Shimazawa, M. , Nakamura, J. and Hara, H. (2016) The Novel cPLA2 Inhibitor AK106-001616 Has a Protective Effect on SOD1^G93A-Induced Cell Death in NSC34 Murine Motor Neuron-Like Cell. Pharmacology & Pharmacy, 7, 193-199. doi: 10.4236/pp.2016.75025.