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**15** 

**Parkinson's Disease** 

*Nagoya University,* 

*Japan* 

α*-*

Toshiharu Nagatsu2,3 and Makoto Sawada3

*4Department of Neurology, Okazaki City Hospital,* 

*-synuclein*), PARK5 (*UCHL-1*), PARK6 (*PINK1*), PARK7

*1Department of Medical Technology, Kobe Tokiwa University,* 

**Role of Microglia in Inflammatory Process in** 

Hirohide Sawada1,2, Hiromi Suzuki3, Kenji Ono3, Kazuhiro Imamura4,

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD). PD is characterized by degeneration and cell death in dopaminergic neurons in the substantia nigra pars compacta (SNpc) and loss of their nerve terminals in the striatum (putamen and caudate nucleus), accompanied by the depletion of the neurotransmitter dopamine (DA) in the striatum. This depletion causes motor symptoms, i.e., resting tremor, muscle rigidity, and akinesia. The level of tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine (DA, noradrenaline, and adrenaline) synthase in the nigro-striatal region of PD patients is decreased (Nagatsu and

A small percentage of PD is familial with a hereditary history. However, most cases of PD (approximately 90-95 %) are sporadic without any hereditary history. In 2009, 16 causative genes of familial PD have been identified (Satake et al., 2009), including PARK1 (

(*DJ-1*), PARK8 (*LRRK2*), and PARK9 (*ATP13A2*). Sporadic PD and some cases of familial PD are characterized by the presence of cytoplasmic inclusions named Lewy bodies, which consist mainly of α-synuclein protein, the product of the PARK1 gene. α-Synuclein is observed not only in PD but also in various neurodegenerative diseases, such as dementia

Based on their investigation of the distribution of α-synuclein-positive Lewy bodies and Lewy neurites in PD patients, Braak et al. (2003) proposed a hypothesis that the pathological process of PD starts first from the lower brain stem and then spreads to the midbrain, limbic system, and cerebral cortex. α-Synuclein-positive inclusions are observed in the anterior olfactory nucleus, dorsal motor nucleus of vagus nerves, and also in peripheral autonomic neurons including those of the sympathetic ganglia, adrenal medulla, and intestinal Auerbach's plexus. Braak et al. (2003) proposed that symptoms of PD appears when Lewy

α

bodies are formed in dopaminergic neurons in the substantia nigra (SN) .

**1. Introduction** 

Sawada M., 2007).

**1.1 What is Parkinson's disease** 

*synuclein*), PARK2 (*parkin*), PARK4 (

with Lewy bodies (DLB).

*2Department of Pharmacology, School of Medicine, Fujita Health University, 3Department of Brain Life Science, Research Institute of Environmental Medicine,* 

