Cell biology of protein misfolding: the examples of Alzheimer's and Parkinson's diseases.
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.
Selkoe
Dennis J
DJ
Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. dselkoe@rics.ewh.harvard.edu
D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D000595:Amino Acid Sequence; D006801:Humans; D008969:Molecular Sequence Data; D010300:Parkinson Disease / Q000473:pathology* / Q000503:physiopathology; D010641:Phenotype; D017510:Protein Folding