title: Catecholamines and Neurodegeneration in Parkinson's Disease-From Diagnostic Marker to Aggregations of α-Synuclein.
abstract: Parkinson's disease is the second most prevalent disease of the brain. It is characterized by midbrain dopaminergic neuronal degeneration accompanied by Lewy bodies, intra-cytoplasmic neuronal inclusions that consist mainly of alpha-synuclein. The cardinal motor features are muscular rigidity, bradykinesia, and resting tremor and, in advanced cases, postural instability. Symptoms are relieved by dopamine replacement therapy, but progress slowly. Clinical diagnosis is made according to medical history, neurological examinations and the response to anti-Parkinsonian drugs. There are no laboratory tests for diagnosis of the disease; however, for development of disease-modifying treatment, early diagnosis by objective laboratory test is required. Recently, postsynaptic sympathetic norepinephrine nerve terminals were found to be degenerated as well as mesencephalic dopaminergic neurons. Cardiac norepinephrine denervation can be seen by meta-iodine-benzyl guanidine scintigraphy, and may be a reliable diagnostic marker. Degeneration of norepinephrinergic and dopaminergic neurons suggests that catecholamines may play a central role in the neurodegeneration in Parkinson's disease. Recently several studies showed that alpha-synuclein aggregates in cells exposed to dopamine. Here, we review findings relating to an early diagnostic marker for detecting degeneration of the peripheral sympathetic nerves, and propose the hypothesis that catecholamines cause alpha-synuclein to aggregate and play an important role in disease pathogenesis.
authors.affiliation: Clinical Research Center, Utano National Hospital, National Hospital Organization, 8 Ondoyama-cho, Narutaki, Ukyoku, Kyoto 616-8255, Japan. sawada@unh.hosp.go.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sawada
authors.affiliation: Clinical Research Center, Utano National Hospital, National Hospital Organization, 8 Ondoyama-cho, Narutaki, Ukyoku, Kyoto 616-8255, Japan. mlb36641@nifty.com.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Oeda
authors.affiliation: Clinical Research Center, Utano National Hospital, National Hospital Organization, 8 Ondoyama-cho, Narutaki, Ukyoku, Kyoto 616-8255, Japan. kyama1024@yahoo.co.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamamoto
keywords: aggregation; biomarker; disease-modifying; neuroprotection; α-synuclein
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