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Cell biology of protein misfolding: The examples of Alzheimer's and Parkinson's diseases

Abstract

The salutary intersection of fundamental cell biology with the study of disease is well illustrated by the emerging elucidation of neurodegenerative disorders. Novel mechanisms in cell biology have been uncovered through disease-orientated research; for example, the discovery of presenilin as an intramembrane aspartyl protease that processes many diverse proteins within the lipid bilayer. A common theme has arisen in this field: normally-soluble proteins accumulate, misfold and oligomerize, inducing cytotoxic effects that are particularly devastating in the post-mitotic milieu of the neuron.

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Figure 1: A model of key events underlying the pathogenesis of Alzheimer's disease, based on available evidence.
Figure 2: Schematic diagrams of the β-amyloid precursor protein (APP) and its principal proteolytic derivatives.

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D.J.S. is a founding scientist of Athena Neurosciences and consultant to Elan Plc.

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Selkoe, D. Cell biology of protein misfolding: The examples of Alzheimer's and Parkinson's diseases. Nat Cell Biol 6, 1054–1061 (2004). https://doi.org/10.1038/ncb1104-1054

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