Misfolding diseases

In recent years it has become evident that impaired protein folding plays a key role in a wide variety of diseases. The misfolding diseases can for simplicity be divided into three main categories:

1. Gain-of-toxic-function diseases (e.g. amyloid diseases)
2. Infectious protein misfolding (the prion diseases)
3. Loss-of-function diseases (e.g. marble brain syndrome, MBS)

There are considerable overlaps between these categories and in many cases it is not clear which of the mechanisms that are the dominating cause of pathology. In my view it is therefore important to have a holistic view of the folding and misfolding areas to understand the molecular basis underlying these diseases. Common denominators for these proteins are: Aberrant folding, partially folded intermediates, conformational plasticity and protein aggregation.

Table: Three classes of misfolding diseases

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Last updated: 2010-02-08