All neurodegenerative conditions are caused by loss of function and the death of certain neurons in the brain (hence the name “neurodegeneration”). Depending on which specific neurons get affected, the conditions can manifest themselves very differently. Neurodegeneration leads to dementia in the case of Alzheimer’s disease or causes gradually worsening problems with motor functions in patients with Parkinson’s disease.
However, the loss of neurons is not the only common feature of all these conditions. The most common neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s all have another common feature: they are caused by an accumulation of very specific and rather unusual forms of proteins called prions.
Although prions lack the complexity of viruses and bacteria, they act similar to infectious agents.
The common mechanism in the development of neurodegenerative conditions
Prions are misfolded versions of some proteins that occur in our body naturally. A very unusual feature of the prions is their ability to act as catalysts of their own formation. When such misfolded protein molecule interacts with a normally folded version of the same protein, it can change its configuration and transform it into a misfolded configuration. Misfolded configurations of prions are more stable, and a single molecule of prion can act as a seed for the formation of other prions from the normally functioning versions of prion’s precursor.
Once a single prion molecule gets into a cell or becomes formed there, it transforms many other normal proteins into the abnormal configuration. If there is a mechanism to bring a prion from one cell to another (or from one organism to another), the spread of prions manifests itself as an infection. In recent decades, neuroscientists have demonstrated that prions can indeed be transferred from one neuron to another through axons connecting the nerve cells.
This is how a prion infection, once started, spreads between the brain cells. The accumulation of prion molecules is usually accompanied by the formation of insoluble aggregates, as these misfolded proteins tend to be insoluble. The precipitates further affect the normal functioning of neurons.
Can a vaccine prevent the development of dementia?
The misfolded proteins found in neurodegenerative conditions have specific structural features called beta-sheets. These structural features are common in all misfolded proteins regardless of their origin. More importantly, these structures can be recognized by our immune system.
Scientists are working on a vaccine that would recognize this feature and then trigger the immune system to remove the misfolded proteins. There are several challenges to overcome here.
First, our immune system does not recognize small molecules, which means that the target of vaccine should be a prion molecule of substantially large size. However, the prions that are too large and not soluble could not be handled successfully by the immune system either. The solution is to target the so-called oligomers, the agglomerates of several misfolded proteins that are large enough to be recognized by the immune system but not too large to become insoluble.
The second challenge is to make sure that normal proteins with similar structural features are not affected. Although the protein structures containing beta-sheets are very rare, there are similar protein structures that can mislead the immune system. A possible solution here is to create a vaccine that targets a specific protein sequence within the beta-sheet structure.
If successful, the strategy may help to create a treatment that would work for all major neurodegenerative diseases. This is a great advantage, as many of these diseases are characterized by the misfolding of several proteins. In Alzheimer’s disease, for instance, amyloid-beta and tau protein are misfolded and form agglomerates. Targeting just a single pathological agent could only provide a limited positive outcome.
Although we still have no cure for neurodegenerative diseases, early signs of dementia linked to these conditions can be detected using the BrainTest® app. Early detection is vital for successful management of these conditions.