The Role of Micrornas in Alpha-1 Antitrypsin Deficiency Disease.

TL;DRAbstract

The hereditary disorder alpha-1 antirypsin deficiency (AATD) results from mutations in the SERPINA1 gene. The most common form of AATD occurs because of the Z mutation causing the protein to fold aberrantly and accumulate in the endoplasmic reticulum (ER) as opposed to being secreted into the circulation. The loss-of-function of AAT in neutralising neutrophil elastase and other proinflammatory enzymes contribute to the pathogenesis of emphysema. Meanwhile, the gain-of-function effects are thought to derive from the toxicity of the ZAAT forming insoluble polymers within hepatocytes leading to liver disease. The unfolded protein response (EIPR), a component of the ER stress has been shown to occur in monocytes due to ZAAT accumulation intracellularly. In view of both loss-and gain-of-function effects, numerous strategies have been examined for the development of gene therapies to address both aspects of the disease. MicroRNAs (miRNAs) are small non-coding RNAs that regulate expression by

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