Switch off Alzheimer’s with Riboswitches

Alzheimer’s is an old age problem commonly referred to as forgetfulness. It is caused by the accumulation of amyloid and tau proteins in the brain. Reportedly, it occurs in aged people usually after the sixties. Both men and women are equally prone to this disease. Amyloid and tau proteins are chemically lipoproteins that get conjugated with lipids. As a result of an accumulation of these proteins, the brain starts to shrink which is referred to as brain atrophy. Hence, due to protein buildup, the neuron network gets disconnected. These neuron connections are involved in memory and learning.

A diagram showing a healthy brain and a brain that has been affected by Alzheimer's and shows signs of decay. — Effect of Alzheimer’s on the brain. *Image source: National Institute of Aging*

Alzheimer’s patients are usually reported to forget things and cannot develop connections to events. I have an Alzheimer’s patient in my family. She barely remembers anything. The life of such patients becomes miserable. So far, no treatment is available for this disease. In this article, a strategy is proposed which might serve as a treatment regime i.e., through Riboswitches. Riboswitches are found in prokaryotes (small unicellular organisms such as bacteria, viruses etc.) They are untranslated regions in the messenger RNA of prokaryotes that can be modified and used in human beings for controlling genes. As they are the components of cellular machinery, they have the potential to turn the genes on or off.

A diagram that shows how the RNA riboswitch mechanism works to inhibit production of the protein that causes Alzheimer's. — Control of the translation process by Riboswitches. *Image source: IGEM*

The riboswitches are composed of two main components: an aptamer and a regulatory part. The aptamer binds a specific ligand and switches the gene expression on or off. Moreover, it holds the Ribosome Binding Site (RBS) where the ribosome binds for protein synthesis. This strategy can probably be used for Alzheimer’s treatment. Neuron networking is required for memory and learning and hence both of these are affected in Alzheimer’s patients. The Riboswitches can be used to control the messenger RNA for tau and amyloid protein synthesis. In the presence of an excess of these toxic proteins the aptamer can be designed to hold the RBS without which the mRNA cannot synthesize proteins. Hence the toxic protein in Alzheimer’s patients can be controlled by using Riboswitches.

The Riboswitches can be designed using the 5’ untranslated region of the messenger RNA of prokaryotes. The aptamer is such that it recognizes a signal/ligand and responds to it. It also responds to the specific concentration of a substance. Since the concentration of tau and amyloid proteins is elevated in Alzheimer’s therefore the aptamer can be designed according to a specific concentration limit. When the aptamer recognizes that specific concentration limit it binds to the P site which is the RBS in humans. Methionine is the first amino acid that is incorporated into the start codon AUG of the mRNA by the transfer RNA. The aptamer can be designed to hold the P site when the amyloid and tau protein concentration is in excess. In this way, the protein synthesis can be stopped which is the underlying cause of Alzheimer’s.