Background:
Protein kinases are the enzymes involved in phosphorylation of different proteins which
leads to functional changes in those proteins. They belong to serine-threonine kinases family and are classified
into the AGC (Protein kinase A/ Protein kinase G/ Protein kinase C) families of protein and Rho-associated
kinase protein (ROCK). The AGC family of kinases are involved in G-protein stimuli, muscle contraction, platelet
biology and lipid signaling. On the other hand, ROCK regulates actin cytoskeleton which is involved in the
development of stress fibres. Inflammation is the main signal in all ROCK-mediated disease. It triggers the cascade
of a reaction involving various proinflammatory cytokine molecules.
Methods:
Two ROCK isoforms are found in mammals and invertebrates. The first isoforms are present mainly in
the kidney, lung, spleen, liver, and testis. The second one is mainly distributed in the brain and heart.
Results:
ROCK proteins are ubiquitously present in all tissues and are involved in many ailments that include
hypertension, stroke, atherosclerosis, pulmonary hypertension, vasospasm, ischemia-reperfusion injury and heart
failure. Several ROCK inhibitors have shown positive results in the treatment of various disease including cardiovascular
diseases.
Conclusion:
ROCK inhibitors, fasudil and Y27632, have been reported for significant efficiency in dropping
vascular smooth muscle cell hyper-contraction, vascular inflammatory cell recruitment, cardiac remodelling and
endothelial dysfunction which highlight ROCK role in cardiovascular diseases.
Thiol protease inhibitors (cystatins) are implicated in various disease states from cancer to neurodegenerative conditions and immune responses. Cystatins have high amyloidogenic propensity and they are prone to form fibrillar aggregates leading to amyloidosis. Particularly challenging examples of such disorders occur in type 2 diabetes, Alzheimer's and Parkinson's diseases. The aim of the present study is to find an interaction between the compound methylglyoxal (MG) which is particularly elevated in type 2 diabetes with caprine brain cystatin (CBC). Results have shown that elevated concentration of MG forms amyloid aggregates of CBC. This was achieved by allowing slow growth in a solution containing moderate to high concentrations of MG. When analysed with microscopy, the protein aggregate present in the sample after incubation consisted of extended filaments with ordered structures. This fibrillar material possesses extensive β-sheet structure as revealed by far-UV CD and IR spectroscopy. Furthermore, the fibrils exhibit increased Thioflavin T fluorescence.
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