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**9** 

*China* 

*Xuzhou Medical College* 

**Actions of GDNF on Midbrain Dopaminergic** 

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

Parkinson's disease (PD) is also known as paralysis agitans. As a degenerative disease of the central nervous system (CNS), PD is characterized by static tremors, bradykinesia, myotonia and unstable posture. It is a disease normally occurring in older adults, especially after the age of 60. Thus far, the etiology and mechanisms underlying this disease have not been fully elucidated (Daly *et al.*, 1999), though most scholars support the dopamine hypothesis and the oxidative stress hypothesis of PD. According to the dopamine hypothesis, dopamine synthesis decreases following the pathologic degeneration of DA-ergic neurons in the substantia nigra pars compacta (SNpc), leading to a decrease in inhibition of acetylcholine in the corpus striatum and a relative increasing excitability of acetylcholine. The disequilibrium between dopamine and acetylcholine results in the hyper-functioning of the extrapyramidal system, thus leading to paralysis agitans. The oxidative stress hypothesis explains the causes of degeneration of DA-ergic neurons in the SNpc. In PD, hydrogen peroxide (H2O2) and superoxide anions, produced during the process of oxidative metabolism under oxidative stress, are catalyzed by Fe2+ in the SNpc, and then formed into hydroxy radicals with more significant noxious properties. Meanwhile, the activity of complex I of the mitochondrial respiratory chain in DA-ergic neurons decreases, causing

factors and PD treatments, and the mechanisms of action of GDNF.

**2. Parkinson's disease and neurotrophic factors** 

**1. Introduction** 

**2.1 Parkinson's disease** 

**Neurons: The Signaling Pathway** 

Dianshuai Gao, Yi Liu, Shen Sun, Li Li and Ye Xiong

