Serpinopathies and the conformational dementias.
The serpin superfamily of serine proteinase inhibitors has a central role in controlling proteinases in many biological pathways in a wide range of species. The inhibitory function of the serpins involves a marked conformational transition, but this inherent molecular flexibility also renders the serpins susceptible to point mutations that result in aberrant intermolecular linkage and polymer formation. The effects of such protein aggregation are cumulative, with a progressive loss of cellular function that results in diseases as diverse as cirrhosis and emphysema. The recent recognition that mutations in a serpin can also result in late-onset dementia provides insights into changes that underlie other conformational diseases, such as the amyloidoses, the prion encephalopathies and Huntington and Alzheimer diseases.
D000682:Amyloid / Q000378:metabolism; D000818:Animals; D003704:Dementia / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D000071058:Huntingtin Protein; D002479:Inclusion Bodies / Q000235:genetics; D008958:Models, Molecular; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011328:Prions / Q000378:metabolism; D011487:Protein Conformation; D015843:Serpins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000097522:Neuroserpin
D000682:Amyloid; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D009687:Nuclear Proteins; D011328:Prions; D015843:Serpins; D000097522:Neuroserpin; C086055:HTT protein, human