Carbenoxolone Exerts Neuroprotection in an Animal Model of Parkinson's Disease Induced by Proteasome Inhibitor MG-132

Department of Biophysics, Panjab University, Chandigarh-160014, India

# contributed equally to work

^* Corresponding author

Dr. Bimla Nehru

Department of Biophysics

Panjab University

Chandigarh-160014

India

Phone: +91 0172 2534128

Email: bnehru@pu.ac.in

Abstract

Dysfunctions of ubiquitin proteasome system (UPS), intracellular protein degradation mechanism lead to the aggregation of aberrant proteins, which is a hallmark of Parkinson's disease (PD). Heat shock proteins (HSP) assist in refolding of misfolded proteins and in proper functioning of UPS. Thus, the neuroprotective potentials of carbenoxolone (Cbx), a HSP inducer were evaluated in a PD model generated by a single intranigral injection of a proteasome inhibitor MG-132 into rat brains. Cbx (20 mg/kg body weight) was given as post-treatment for 12 days. MG-132 destroyed dopaminergic neurons causing loss of dopamine and tyrosine hydroxylase (TH) that resulted in impaired motor functions. Elevations in the markers of oxidative stress like LPO (Lipid peroxidation), protein carbonyl, NO (Nitric oxide) and citrulline was also observed in MG-132 treated animals. However, induction of HSP-70 by Cbx helped to combat the toxicity caused by proteasome inhibition. Reduction in oxidative stress was also observed after Cbx co-treatment which helped in preventing neuronal cell death. As a result, improvements in the dopamine levels and associated motor functions were also observed. Thus, all the assessed parameters provide the clear evidence that Cbx is a potential neuroprotector for PD.

Keywords: UPS dysfunction; Carbenoxolone; Oxidative stress; Motor functions.

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