Alzheimer’s Disease in the year 2014 alone cost £24.2 billion (UK), but what can be done?
Alzheimer’s Disease is defined by mass cerebral atrophy i.e. the loss of brain volume, alongside the deposition of an amyloid precursor protein, and the formation of a tangle within neurons due to the over modification of a second tau protein.
In healthy individuals, the amyloid precursor protein is processed at a certain position in the protein sequence to form two products, both of which have no effect on the body. However in Alzheimer’s Disease, this same protein is processed at an alternative position leading to the formation of two products, where one of these proteins negatively affects the body. This protein sticks to other proteins to form a protein plaque which causes the death of neurons.
In health, tau binds the microtubule to stabilize it. In Alzheimer’s Disease, the tau protein becomes altered, so tau can no longer bind the microtubule. Microtubules form long string-like structures in neurons, so when the tau can no longer bind, these structures intertwine with one another to form tangles, and result in the death of these neurons.
The treatment as of now for Alzheimer’s Disease focuses on inhibiting cholinesterase. Cholinesterase is an enzyme which breaks down acetylcholine. The neurons which die in Alzheimer’s Disease release acetylcholine, so the treatment as of current aims to maximise acetylcholine levels by inhibiting the breakdown, to act as a compensatory method for the loss of acetylcholine producing neurons.
So what is the issue with this treatment? The treatment as described is not a cure but instead only provides symptomatic relief to those with Alzheimer’s Disease.
It is thereupon essential to take an alternative approach to treating Alzheimer’s Disease. There is a region within the neuronal cell body named the endoplasmic reticulum. The endoplasmic reticulum functions in the synthesis of proteins, and ensures these proteins are in the correct shape. In Alzheimer’s Disease, the tau proteins being modified, and the formation of the protein plaque, means proteins are not in the correct shape, thereafter this induces a state of stress.
Stress in the endoplasmic reticulum has implications on the unfolded protein response pathway. The activation of this pathway leads to one of two outcomes; neuronal cell death, or a reduction in the endoplasmic reticulum stress. In Alzheimer’s Disease due to the abundance of proteins in an incorrect shape, this pathway becomes dysfunctional and the output switches to neuronal cell death. It is this neuronal cell death caused by the protein plaques and neuronal tangles, as described previously, responsible for Alzheimer’s Disease. It is therefore possible to target a certain aspect of this unfolded protein response pathway to inhibit the cell death responsible for Alzheimer’s Disease, and thereupon treat the disease.
Is targeting the unfolded protein response pathway the future for those with Alzheimer’s Disease? We can hope.
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