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Dopamine and Parkinson's disease: is the killer in the house?

Molecular Psychiatry volume 8, pages 369–370 (2003)Cite this article

One of the most striking features of Parkinson's disease is that it primarily affects a restricted neuronal population in the brain. Although other neurons are also affected, the dopaminergic neurons of the substantia nigra pars compacta are the most vulnerable to the disease process. The reason for this selective cell loss remains unknown. It has long been suspected that high levels of dopamine in these neurons may put them at risk. A recent study by the group of Bruce Yankner at Harvard Medical School and the Children Hospital in Boston proposes a mechanism by which dopamine may contribute to the selective vulnerability of nigrostriatal dopaminergic neurons in Parkinson's disease.1

Novel insights into the pathophysiology of Parkinson's disease have emerged in the last 4–5 years from the realization that alpha-synuclein, a protein mutated in rare forms of familial Parkinson's disease,2 is a major component of the Lewy bodies, the characteristic inclusions present in the dopaminergic neurons of patients with Parkinson's disease.3 Accumulation of alpha-synuclein is not specific of Parkinson's disease. It also occurs in dementia with Lewy bodies and multisystem atrophy,4 suggesting a common link between these various neurodegenerative pathologies that are now grouped under the name ‘synucleopathies’.4 Synuclein normally associates with synaptic vesicles and seems to play a role in synaptic function.5 Why this normally amorphous protein forms aggregates in these pathological situations is not fully understood. The presence of nitrated forms of synuclein in Lewy bodies, axons, and dendrites of affected neurons suggests that oxidative stress may alter the conformation of the protein, leading to the formation of fibrillar aggregates.4 Alpha-synuclein may also form pores that could play a role in toxicity.6

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  1. Department of Neurology, The Geffen School of Medicine at UCLA, CA, USA

    M-F Chesselet

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  1. M-F Chesselet
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Correspondence to M-F Chesselet.

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Chesselet, MF. Dopamine and Parkinson's disease: is the killer in the house?. Mol Psychiatry 8, 369–370 (2003). https://doi.org/10.1038/sj.mp.4001289

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