O'Suilleabhain PE, Sung V, Hernandez C, Lacritz L, Dewey RB, Bottiglieri T, Diaz-Arrastia R.
Elevated plasma homocysteine level in patients with Parkinson disease: motor, affective, and cognitive associations.
Arch Neurol. 2004 Jun;61(6):865-8.
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What a great group of papers...
From my perspective, the most thrilling paper is the one from Kevin McNaught and colleagues. It is important because it tests the idea that proteasome dysfunction is central to cell damage and inclusion formation in PD and related disorders. A problem with this idea is that although dopaminergic neurons do appear to be susecptible to this type of damage, there are reports that decreased proteasome function also occurs in other diseases that may or may not have a parkinsonian component (e.g., the polyglutamine diseases or ALS). Therefore, unless one looks at the whole nervous system one cannot be sure that proteasome inhibition is a sufficient explanation for PD, and not a general facet of neurodegenerative diseases. The McNaught paper directly addresses this, and as a bonus may provide us with an easily replicable model that has both neuronal loss and inclusion formation - something that has been lacking to date. The challenge for the community will be to replicate the current methods and expand them into other areas - finding out whether this works, for example, in mice would be helpful to start testing ideas in transgenic and knockout animals.