Progerin

Progerin is a truncated version of lamin A protein involved in Hutchinson-Gilford progeria syndrome. Progerin is most often generated by a mutation (C1824T) in the lamin A gene, LMNA. This mutation activates a cryptic splice site and gives rise to a form of lamin A with a deletion of 50 amino acids.cite journal |author=Eriksson M, Brown WT, Gordon LB, "et al" |title=Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome |journal=Nature |volume=423 |issue=6937 |pages=293–8 |year=2003 |month=May |pmid=12714972 |doi=10.1038/nature01629 |url=] Approximately80% of Hutchinson-Gilford progeria syndrome cases carry a single copy of the most common mutation, a silent point mutation (G608G) within exon 11 of LMNA gene. [cite journal |author=McClintock D, Gordon LB, Djabali K |title=Hutchinson-Gilford progeria mutant lamin A primarily targets human vascular cells as detected by an anti-Lamin A G608G antibody |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=103 |issue=7 |pages=2154–9 |year=2006 |month=February |pmid=16461887 |pmc=1413759 |doi=10.1073/pnas.0511133103 |url=]

Lamin A constitutes a major structural component of the lamina, a scaffold of proteins found inside the nuclear membrane of a cell; progerin 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.cite web |url=http://www.sciencedaily.com/releases/2005/08/050830065132.htm |title=Anti-cancer Drugs May Hold Promise For Premature Aging Disorder |format= |work= |accessdate=2008-07-15] Researchers have shown that progerin activates genes that regulate stem cell differentiation via the Notch signaling pathway.

Researchers are exploring farnesyltransferase inhibitors as a potential pharmacological therapy against the negative effects of progerin on nuclear morphology.

Progerin, which has been linked to normal aging, is produced in healthy indivduals via "sporadic use of the cryptic splice site".cite journal |author=Scaffidi P, Misteli T |title=Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing |journal=Nat. Cell Biol. |volume=10 |issue=4 |pages=452–9 |year=2008 |month=April |pmid=18311132 |pmc=2396576 |doi=10.1038/ncb1708 |url= cite web |url=http://www.eurekalert.org/pub_releases/2008-03/nci-asc022908.php |title=Adult stem cell changes underlie rare genetic disease associated with accelerated aging |format= |work= |accessdate=2008-07-15] [cite journal |author=Liu B, Zhou Z |title=Lamin A/C, laminopathies and premature ageing |journal=Histol. Histopathol. |volume=23 |issue=6 |pages=747–63 |year=2008 |month=June |pmid=18366013 |doi= |url=http://www.hh.um.es/Abstracts/Vol_23/23_6/23_6_747.htm]

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