In recent years researchers have focused on the identification of genes that play a role in the aging process and age-related diseases. One such illnesses is Hutchinson-Gisford Progeria Syndrome, also known as progeria. The cause of progeria is single-nucleotide polymorphism in 1824 position in gene LMNA, that codes nuclear protein lamin A.
|Hutchinson-Gilford Progeria Syndrome|
The nuclear lamina is the structural support of the nucleus and it serves as the scaffold for DNA-protein interactions. Given that the nuclear lamina is involved in a wide array of biological processes, including DNA replication, transcription, cell cycle progression, and chromatin organization, it is not surprising that alterations in the proteins that make up this structure would have significant deleterious effects and give rise to diseases. The diseases that are associated with defects in the lamin proteins that compose the nuclear lamina are referred to as laminopathies. Lamin A is one of the lamin proteins that has been shown to be highly mutated; to date, over 400 point mutations have been identified in lamin A. Genetic alterations of the lamin A gene contributes to laminopathies and aging-related diseases, which makes lamin A a viable target for the treatment these diseases.
The biological effects of genetic alterations in lamin A are not only related to the mutations in the lamin A gene, but also to the balance of normal lamin A proteins to mutated lamin A proteins within the cell.
|Functions of nuclear lamina (Travis A Dittme and Tom Misteli, 2011).|
So the optimal therapeutic strategy for laminopathies and aging-related diseases that are linked to lamin A should be a multifaceted approach that targets lamin A at a genetic level in combination with downstream cell signaling and cellular processes approaches. Our computation analysis project identified signaling pathways that regulated lamin A expression as well as lamin A - protein interactions that mediated diseases. To date, this is the first study of its kind to identify these 12 potential treatment strategies for laminopathies and diseases related to aging: (1) IGF-1/GH balance restorers, (2) Notch inhibitors, (3) reactive oxygen species scavengers, (4) telomerase activators, (5) Rb inhibitors, (6) apoptosis inhibitors, (7) translation- and autophagy-activator inhibitors, (8) cAMP activators, (9) thyroid hormone supplements, (10) PI3K inhibitors, (11) epigenetics marks reversal, and (12) farnesylation inhibitors.
|Signaling pathways in which LMNA gene is involved|
However, further trials are needed to validate these treatments and to determine their efficacy in a clinical setting.
You can read full article on the link: http://link.springer.com/article/10.1007/s00109-012-0962-4