Can we potentiate aberrant isoforms?


Splicing mutations resulting in a stop codon lead to the synthesis of
aberrant CFTR. Usually, the sooner in the aminoacidic strain the error occurs,
the less "normal chain" is built.
For splicing mutations with sites of alteration falling after the
R-Domain portion (see Figure), we'll find an aberrant protein lacking
just the TM2-NBD2 terminal portion.
Scientists are still debating about the necessity of these final
portions, somebody thinking these are essential for the protein to
work, other thinking their job is just to stabilize the first portion
of CFTR.
In this respect, It is interesting to note that even splicing
mutations producing aberrant NBD1-TM1-R domain protein, translate into
a milder phenotype with less gastro-intestinal issues.
This is surprising, as these splicing mutations fall before the
R-Domain portion, which means they lead to an even shorter correct
aminoacidic strain.
So it's still unclear if even the first truncated part of CFTR is
able, alone, to let pass some anions, such as HCO3-, leading to lower
gastro-intestinal complications and improved pulmonary conditions.
Therefore an interesting question is: Can aberrant proteins be
potentiated? And if so, which one of them?

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