Abstract

Parkinsons disease (PD) is generally a sporadic disease, and only a small proportion of cases have a clear genetic component. During the last few years, a possible specific cause triggering death of dopaminergic neurons in the substantia nigra, drug of abuseinduced neurotoxicity, is being considered as a potential mechanism to develop PD, especially in the case of abuse of amphetamine and its derivatives. Recent evidences have shown pleiotrophin, a growth factor with important functions in remodeling and repair of injured neural tissue, as an important factor involved in the pathogenesis of both diseases by preventing neurodegeneration in Parkinsons disease, neurotoxicity induced by drug abuse and by its ability to modulate drugs addictive effects. This review discusses targeting growth factors such as glial-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) to treat Parkinson ’ s disease and/or drug addiction and compiles recent evidences to propose the pleiotrophin/receptor protein tyrosine phosphatase β/ζ signaling pathway as a new therapeutic target to treat Parkinsons disease and to prevent drug of abuse-induced neurotoxicity and addictive effects.

Keywords: Pleiotrophin, midkine, drug abuse, neurodegeneration, GDNF, beta-catenin