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.
Highlights
Parkinson’s disease is characterized by mesencephalic nigral dopaminergic neuronal degeneration accompanied by Lewy bodies, intra-cytoplasmic neuronal inclusions that consist mainly of insoluble aggregated alpha-synuclein [1,2,3]
Cardinal motor features are bradykinesia, muscular rigidity and resting tremor that are caused by dopamine depletion in the striatum owing to a loss of projections from mesencephalic dopaminergic neurons
The molecular mechanisms by which brain dopaminergic neurons degenerated have not been elucidated, catecholamines may be a key molecule in the degenerative process
Summary
Parkinson’s disease is characterized by mesencephalic nigral dopaminergic neuronal degeneration accompanied by Lewy bodies, intra-cytoplasmic neuronal inclusions that consist mainly of insoluble aggregated alpha-synuclein [1,2,3]. At the end of the open-label period, there would be a difference in effects between the early-start and delayed-start groups if the intervention has disease-modifying effects. Rasagiline, an inhibitor of brain monoamine oxidase, improves the symptoms and signs of Parkinson’s disease It enhances dopaminergic neuronal transmission because it blocks dopamine degradation by brain monoamine oxidase, and the effects are taken to be symptomatic. It may provide neuro-protective effects by inhibition of production of harmful molecules such as methyphenyl pyridinium [16], or promotion of mitochondrial viability [17]. 1,176 untreated Parkinson’s disease patients were enrolled and randomized to early-start and delayed-start groups to investigate the effects of 1 mg and 2 mg rasagiline. Though the reason why the result of ADAGIO study was controversial in spite of a large size of the participants has not been fully elucidated, it might be due to the initiation of interventions would be too late to demonstrate disease-modifying effect, even in early-start group
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