Actions of GDNF on Midbrain Dopaminergic Neurons: The Signaling Pathway

Parkinson's disease (PD) is a degenerative disease of the central nervous system (CNS) predominantly occurring in older adults, and is particularly common after the age of 60. The primary pathologic characteristics of PD are neuronal degeneration and cell death of dopaminergic (DA-ergic) neurons, leading to a decrease in the dopamine (DA) level in the striatum. Originally extracted and purified in 1993, glial cell line-derived neurotrophic factor (GDNF) is a novel neurotrophic factor which exerts neurotrophic effects upon DAergic neurons in the midbrain, sympathetic neurons in the superior cervical ganglion and motor neurons in the spinal cord. Specially, GDNF protects midbrain DA-ergic neurons, and promotes their differentiation and survival (Lin et al., 1993). These studies provide impetus to delve more deeply into the underlying mechanisms of GDNF, and suggest potential future applications of GDNF. The present review focuses on the correlates of neurotrophic factors and PD treatments, and the mechanisms of action of GDNF.