Normal (left) prelamin A processing and the faulty processing leading to the creation of<unk>  (right)<unk>  (UniProt# P02545-6) is a truncated version of the lamin A protein involved in the pathology of Hutchinson–Gilford<unk>  syndrome.<unk>  is most often generated by a single nucleotide polymorphism (C1824T) in the gene that codes for Lamin A. This mutation activates a cryptic splice site and gives rise to a form of lamin A with a deletion of 50 amino acids near the C-terminus. Approximately 80% of all Hutchinson–Gilford<unk>  syndrome cases are heterozygous for this deleterious single nucleotide polymorphism within exon 11 of the LMNA gene. Lamin A constitutes a major structural component of the lamina, a scaffold of proteins found inside the nuclear membrane of a cell;<unk>  does not properly integrate into the lamina, which disrupts the scaffold structure and leads to significant disfigurement of the nucleus, characterized by a lobular shape.<unk>  activates genes that regulate stem cell differentiation via the Notch signaling pathway.<unk>  increases the frequency of unrepaired double-strand breaks in DNA following exposure to ionizing radiation. Also overexpression of<unk>  is correlated with an increase in non-homologous end joining relative to homologous recombination among those DNA double-strand breaks that are repaired. Furthermore, the fraction of homologous recombination events occurring by gene conversion is increased. These findings suggest that the normal untruncated nuclear lamina has an important role in the proper repair of DNA double-strand breaks. Lonafarnib (a farnesyltransferase inhibitor) is a potential pharmacological therapy against the negative effects of<unk>  on nuclear morphology in HGPS. As of 2021 it is the only FDA approved treatment for HGPS. Recently, rapamycin has been shown to prevent<unk>  aggregates in cells and hence delay premature aging.<unk> , which has been linked to normal aging, is produced in healthy individuals via "sporadic use of the cryptic splice site".
Progerin
Equilin
Hippulin
Modulin
Immunoevasin
Apolipoprotein
Collectin
Α-Hederin