Avipsha Datta, Department of Biophysics, University of Calcutta
Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder that impairs brain function and memory. Neurons degenerate, disrupting the neural networks and thereby destroys our memory and other important motor functions. AD is thought to be caused by the abnormal build-up of proteins aggregates in and around the brain cells. One of the proteins involved is called amyloid which deposits in the form of plaques around brain cells. The other protein is called tau which deposits in the form of tangles within the brain cells.
What exactly leads to the aggregate of these protein bodies have intrigued the scientists for decades? Various theories have come up, but yet waiting to come to up to a definite cause. One of the latest studies by a group of Japanese researchers has shown that the enzyme MARK4 (Microtubule Affinity Regulating Kinase 4) plays an important role in the aggregation of Tau protein particles.
Under normal conditions, the Tau protein is an important part of the structure of cells or cytoskeleton. MARK 4 helps Tau to detach from the arms of the cytoskeleton or microtubules constantly assembling and disassembling.
But, when a mutation is incorporated in the MARK 4 gene, the problem arises. The Japanese team had artificially introduced a mutation in the MARK4 gene into a transgenic Drosophila fly, capable of expressing human Tau proteins and studied the changes of the protein in vivo.
They observed that this pathological form of Tau had an excess of certain chemical groups that causes it to misfold. It was also observed that the Tau proteins much easily aggregated and were insoluble in detergents. These made it easier for the Tau to form the tangled clumps that caused the neurons to degenerate.
Previously, MARK 4 has also been found to play important roles in a wide range of other diseases which involved aggregation and build-up of other proteins.
MARK4 thus plays a critical role in the onset of AD. The team’s insights might lead to a breakthrough in the development of treatments and preventive measures for these terminal neurodegenerative conditions.
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