Alzheimer’s disease Research Grants Project Proposal

The risk of developing Alzheimer’s disease (AD), a form of dementia in which mental capabilities of an individual rapidly deteriorates, increases with age. Singapore is currently facing an ageing population and if a medical cure is not found soon, the number of cases of dementia patients is expected to increase by approximately 20,000 every 5 years from now. Hence, research is definitely needed in order to learn more about AD and hopefully find a cure.
There are several possible post-translational modification (PTM) mechanisms that modify protein structure and function. 3 of such processes are Phosphorylation, Glycosylation and Proteolysis.
PTM works with other mechanisms to control eukaryotic gene expression. Such mechanisms include alternative splicing, and histone modification. Alternative splicing is the process where exons created during transcription are joined in multiple different ways during RNA splicing. Histone acetylation loosens chromatin structure and enhances transcription, while DNA methylation reduces transcription.

From the Fig 2 above, we can see that the greater the phosphate content in tau protein in the brain, the greater the risk of AD. Hence, excessive phosphorylation increases the risk of AD.
Phosphorylation of tau protein regulates its activity to bind to microtubules and stimulate their assembly. A normal level of phosphorylation is required for tau protein optimal function, whereas tau protein that is excessive phosphorylated loses its biological activity. When the tau protein becomes excessive phosphorylated, they aggregate into filaments in the neurons of individuals resulting in Alzheimer’s disease (AD)
Tau proteins from AD patients were also found to have undergone glycosylation while tau protein from normal brains did not. Hence, we can infer from this two points that glycosylation reduces the dephosphorylation of the tau proteins. Tau proteins are abnormally glycosylated in AD brain which research shows possibly facilitates kinase activity.. This could be due to the Glycosylation increasing kinase activity on tau protein by increasing the affinity of kinases to bind to amino acid residues, threonine and serine, resulting in excessive phosphorylation, thus inhibiting the regulation of many cell processes.
Thus, it is necessary that a research grant should be given for Alzheimer’s research as there are many areas still unknown and it of utmost importance to find a cure for this ever increasing problem.