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Cardiolipin- The role in Parkinson's and Ischemic Heart Disease
Cardiolipin or precisely 1,3-bis(sn-3′-phosphatidyl)-sn-glycerol is a very important part of mitochondria. It is a phoshlipid with a dimeric structure, having four acyl groups and potentially carrying two negative charges. It is found mostly in the mammalian heart than the rest of the organs.
Cardiolipin is part of the normal plasma lipo-proteins. Traditionally it was not considered to be a part of the plasma lipoprotein, but recent research has proved otherwise . It is located on the inner membrane of the mitochondria where it takes part in activation of enzymes involved in oxidative phosphyrlation. Cardiolipin is identified as a integral part of the respiratory chain and it forms a part of the crystals of mitochondrial complex III, complex IV and the ADP-ATP-carrier, and it is known to be essential for the stability of the quaternary protein structure of the last stage which results in ATP production, which is very essential for the cell to function .
It is a known fact that cardiolipins play a active role in oxidative phosphorylation mechanisms that regulate Stage 4 respiratory cycle by returning ejected protons across and over bacterial and mitochondrial membrane phospholipids, and that regulates State 3 respiration through the relative contributions of proteins that transport protons, electrons and/or metabolites. The barrier properties of phospholipid bilayers support and regulate the slow proton leak that is the basis for State 4 respiration. Mitochondrial cardiolipins, especially those with high 18:2 acyl contents, strongly bind many carrier and enzyme proteins that are involved in oxidative phosphorylation, some of which contribute to regulation of State 3 respiration. Role in Parkinson's disease.
Role in Parkinsons Disease
Parkinson's disease could be of two etiologies-1) Vascular 2) Death or depletion of dopaminergic neurons in Substantia Nigra. Cardiolipin is part of the HDL cholesterol and it and enhances the anticoagulation activities of plasma proteins S and activated protein C and would prevent Parkinsons of vascular etiology 4. The most important complex that gets destroyed in the substantia Niagra is CQ 10 (Co-Enzyme Q 10Complex) which is found in the mitochondria along with cardiolipin . The destruction of CQ10 would be reduced if the ample amount of cardiolipin is available. Since cardiolipin forms a component of Complex 3 and Complex 4, it will get oxidized first rather than CQ10. The mitochondria can then replace the cardiolipin needed for Complex3 and Complex 4 from the blood. This will slow down the apoptosis and slow down the progress of disease. Administering CQ 10 has potential side effects as it can be a source of superoxide radicals. At current, treating Parkinsons with CQ10 is not a standard treatment.A combination of CQ10 in appropriate doses and the newly developed cardiolipin analogue could prevent Parkinson's disease in those with family history of the disease and stop the progression in those with the disease. There have been no studies at present that have either monitored the improvement of Parkinsons disease after administering CQ10. There is also new evidence that destruction of cardiolipin in brain cells result in brain tumors .
Role in Cardiac Disease
Cardiolipin is found the most in the heart. With forming the integral structures of the mitochondria of cardiac myocyte, it increases the efficiency of the heart as whole and improves it function. By its anti-coagulating effect in combination with Protein C and Protein S, it would prevent Ischemic Heart Disease . Cardiolipin is beneficial in maintaining the functions of the cardiac myocyte by ejecting protons across the barrier, facilitating its leak back into the matric which results in the production of ATP, stabilizing the structure of the phospholiping bilayer of the mitchondria. Any cell that has enough energy(ATP0) is able to maintain its function. By having adequate supply of cardiolipin, the function of the heart will improve and may prevent ischemic heart disease. The future protocol for management of IHD disease would definitely include a Cardiolipin analogue and CQ 10 along with the regular regimen of drugs used for treatment.
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