Lamin A

Nuclear lamina is a protein scaffold on the inner edge of the nucleus that helps organize nuclear processes such as RNA and DNA synthesis.

preLamin A contains a CAAX box at the C-terminus of the protein (where C is a cysteine and A is any aliphatic amino acids). This ensures that the cysteine is farnesylated, and this allows preLamin A to bind membranes, specifically the nuclear membrane. After Prelamin A has been localized to the cell nuclear membrane the C-terminal amino acids, including the farnesylated cysteine, are cleaved off by a specific protease. The resulting protein is now Lamin A, is no longer membrane-bound and carries out functions inside the nucleus.

In HGPS the recognition site that the enzyme requires for cleavage of Prelamin A to Lamin A is mutated. Lamin A cannot be produced and preLamin A builds up on the nuclear membrane, causing a characteristic nuclear blebbing. This results in the premature aging symptoms of progeria, although the mechanism connecting the misshapen nucleus to the symptoms is not known.

A study which compared HGPS patient cells with the skin cells from LMNA young and elderly human subjects found similar defects in the HGPS and elderly cells, including down-regulation of certain nuclear proteins, increased DNA damage and demethylation of histone leading to reduced heterochromatin. Nematodes over their lifespan show progressive lamin changes comparable to HGPS in all cells but neurons and gametes. These studies suggest that lamin A defects contribute to normal aging.

related story :Premature Oldness ; A Story on Progeria.

Premature Oldness ; A Story on Progeria.

Children with Progeria comes from the Greek in which word pro means 'before', while the word geras means 'old age'. It is also known as Hutchinson-Gilford Progeria Syndrome. It is an extremely rare, fatal generic condition. At present there are 53 known cases of Progeria around the world. There is a reported incidence of Progeria of approximately 1 in every 4 to 8 million new borns. Both males and females run an equal risk of having Progeria. It was first describe in an academic journal by Dr. Jonathon Hutchinson in 1886, and Dr.Hastings Gilford in 1897 - both in England.

In Projeria patients, the cell nucleus has dramatically aberrant morphology rather then the uniform shape typically found in healthy individuals.


CHARACTERISTICS OF PROGERIA

Children with Progeria are born looking healthy and symptoms starts appearing when they are about 10 to 24 months old which are basically related to aging.

signs of progeria include

• Growth failure
  
• Loss of body fat
  
• Loss of hair
• Skins starts to look aged with wrinkles
• Stiffness in joints
  
• Hip dislocation
  
• Generalized atherosclerosis (cardio and heart disease)
• Stroke

Although they may come from varying ethnic back-grounds, children with Progeria have a surprisingly similar appearance. Progeria patients generally die between the age of 8 and 21 - with the average age being 13.

Children who suffer from progeria are genetically susceptible to premature, progressive heart disease. Nearly all Progeria patients die from heart disease. Heart disease is also one of the leading cause of death globally. Children with Progeria commonly experience cardiovascular events, such as hypertension (high blood pressure), stroke, angina, enlarge heart, and heart failure - conditions linked to aging.


CAUSES OF PROGERIA

Exact cause of it still to be known but 90 % of children with Progeria bears mutations on the gene on the gene that encodes Lamin A , a protine that holds the nucleus and maintains its shape. It is believed that the defective lamin A protein makes the nucleus unstable. This instability seems to lead to the process of premature aging among Progeria patients. So the progeria is the rare mutation disease that happens purely by chance. A non-twin sibling runs the same risk of having Progeria as any other child from another family. In about 1 in every 100 cases of HGPS the syndrome is passed down to the next generation within the same family. So Progeria does not seems to appear hereditary.


Treatment hope

The possible treatment therapies are currently under experimental stages. One of the potential treatment is through Farnesyl transferase inhibitors (FTIs) which are used for treating cancer. It might reverse the nuclear structure abnormalities that are believed to cause Progeria. Studies carried out on mice with progeria like sings and symptoms showed that FTIs appeared to offer some improvements.