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Neurodegenerative disease

Pieces of the Parkinson's puzzle

Nature Reviews Neuroscience volume 11, page 787 (2010)Cite this article

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The authors focused on the brainstem as this region, particularly the dorsal motor nucleus of the vagus (DMNV), is thought to be affected early in the disease. Measuring cerebral blood volume using functional MRI provided high-resolution functional maps of the brainstems of human subjects. These showed that patients with Parkinson's disease had decreased cerebral blood volume in the DMNV, suggesting metabolic alterations in this region. By contrast, the inferior olivary nucleus (ION) — a neighbouring region — did not show such changes. Post-mortem analysis of Parkinson's disease brains also showed the DMNV to be positive for aggregates of the protein α-synuclein, which are associated with Parkinson's disease pathogenesis.

Next, using microarrays, the authors showed that ten transcripts were downregulated in the DMNV of Parkinson's disease brains. Of these, the authors further investigated spermidine/spermine N1-acetyltransferase 1 (SAT1). This enzyme — a component of the polyamine pathway — catabolizes spermine and spermidine, which are polyamines that increase α-synuclein aggregation in vitro. Parkinson's disease brains showed decreased SAT1 expression in the DMNV but not in the ION.

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ORIGINAL RESEARCH PAPER

  1. Lewandowski, N. M. et al. Polyamine pathway contributes to the pathogenesis of Parkinson disease. Proc. Natl Acad. Sci. USA 107, 16970–16975 (2010)

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  1. Yukie Ozawa
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Ozawa, Y. Pieces of the Parkinson's puzzle. Nat Rev Neurosci 11, 787 (2010). https://doi.org/10.1038/nrn2945

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