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Review
. 2003 Jan;111(2):145-51.
doi: 10.1172/JCI17575.

Rare genetic mutations shed light on the pathogenesis of Parkinson disease

Ted M Dawson  1 , Valina L Dawson
Affiliations
Review

Rare genetic mutations shed light on the pathogenesis of Parkinson disease

Ted M Dawson et al. J Clin Invest. 2003 Jan.
No abstract available

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Figures

Figure 1
Figure 1
Structure of α-synuclein and a model of α-synuclein aggregation and toxicity. The modular structure of α-synuclein, illustrating the location of familial-associated mutations and other key features of α-synuclein, including the imperfect (KTKEGV) repeats (R), is depicted in the top panel. The bottom panel shows a model of α-synuclein aggregation and toxicity and the proposed factors that enhance (+) or inhibit (–) the formation of toxic aggregated forms of α-synuclein. DA enhances the formation of the protofibrillar form of α-synuclein and prevents it from aggregating into the fibrillar form (not shown).
Figure 2
Figure 2
Structure of parkin and a model of parkin-mediated ubiquitination and its substrates. In the top panel, the modular architecture of parkin is depicted, and the locations of the reported familial-associated disease-causing missense mutations are indicated. Disease-causing deletions, insertions, and frameshifts are not depicted (see text for details). The bottom panel shows a model of parkin-mediated ubiquitination and Lewy body formation. Parkin may play key roles in both ubiquitination and Lewy body formation in conjunction with the E1 ubiquitin-activating enzyme and the E2s UbcH7, UbcH8, UBC6, and UBC7. Nonglycosylated α-synuclein accumulates in Lewy bodies through mechanisms that are not clear, but it may inhibit (–) proteasomal function. Ub, ubiquitin.
See this image and copyright information in PMC

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Publication types