GLUTAMINE REPEATS AS POLAR ZIPPERS - THEIR POSSIBLE ROLE IN INHERITEDNEURODEGENERATIVE DISEASES

Four inherited neurodegenerative diseases are linked to abnormally exp anded repeats of glutamine residues in the affected proteins. Molecula r modeling followed by optical, electron, and x-ray diffraction studie s of a synthetic poly(L-glutamine) shows that it forms beta-sheets str ongly held together by hydrogen bonds. Glutamine repeats may function as polar zippers, for example, by joining specific transcription facto rs bound to separate DNA segments. Their extension may cause disease e ither by increased, nonspecific affinity between such factors or by gr adual precipitation of the affected proteins in neurons.