From AA to ZZ

摘要

Not only who we are, but also what diseases we suffer from is probably written somewhere in our DNA. Some genetic diseases are associated with the aggregation of misfolded mutant pro-teins that are toxic to cells. Quality-control mechanisms ensure that incorrectly folded proteins are usuallyrndegraded. For example, secretory proteins are folded in the endoplasmic reticulum (ER), and defective proteins are sorted and targeted for degradation, which is mediated in part by the enzyme ER mannosidase I (ERManl). A mutated version of the gene encoding alpha-1 anti-trypsin (AAT) is associated with the accumulation of the misfolded Z variant of AAT in the ER and is a risk factor for the development of end-stage liver disease. However, the age of onset of this disease is variable, and other factors may be involved.