Misfolded Proteins or Prion Proteins

Simply put, misfolded proteins are proteins gone rogue. These bad actors drive the progression of neurodegenerative diseases. Tracking the prion biomarkers is a sure-fire way to diagnose Alzheimer’s, Parkinson’s, and other dementias.

To understand prions or misfolded proteins, let’s first understand what normal proteins are.

Proteins are linear chains composed of building blocks called amino acids. Each linear protein chain folds naturally into a unique three-dimensional shape.

Some proteins can misfold into one or more alternative forms. Occasionally, these misfolded shapes may lead to disease. Under rare circumstances, the misfolded proteins may induce the normal forms of proteins to misfold.  These self -replicating and toxic misfolded proteins are called Prions.

Therefore, prions represent normal brain proteins that have misfolded into odd, toxic shapes; think of origami in which we fold a piece of paper into different shapes.

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Prions Are Proteins Gone Rogue.

Watch how the rogue proteins fly under the radar to destroy our brains over decades without the body showing signs of illness or loss of physical/mental abilities.

Misfolded Abeta, Synuclein, and Tau are critical biomarkers for ParkinZheimer spectrum diseases. Learn how these insidious prions damage brain health.

How Prions Damage the Brain

Once protein misfolding is triggered, the prion-protein gains an ability to corrupt other normal proteins to misfold, forming a zombie protein army over time. The zombie protein army continues to expand and multiply, destroying neurons along the way. During this development stage, the body and brain show no symptoms or loss of mental functions.

This asymptomatic stage can last years or multiple decades, slowly damaging the brain under the radar without us knowing. When we finally notice the loss of physical or mental facilities, we go to the doctors for a diagnosis.  It’s already the late stage, as much of the brain has suffered irreversible damage.

The signature characteristic of replication in misfolded proteins appears to play a role in the progression of both Alzheimer’s and Parkinson’s. Unlike Mad Cow Disease, the prion-like properties observed in Alzheimer’s and Parkinson’s are not infectious and cannot spread between people.

Prions are virtually impossible to detect using existing methods in the marketplace, mainly because their basic structure is identical to standard proteins. 

Once the concentration of prions reaches a certain threshold within a brain cell or neuron, it causes cell death.  Unlike most cells in the body, nerve cells in the brain cannot regenerate with newer copies, leading to the unrecoverable loss of mental and motor functions.

Neurodegenerative diseases, as a whole, are associated with misfolded proteins or prions. We use these terms interchangeably throughout the website.

Prion Proteins’ Superpowers

Misfolded proteins can replicate and spread disease by recruiting other normal proteins to misfold. One prion can turn into more than billions of prions over several years. Prion-proteins can move directly from cell to cell or travel through the blood or cerebral spinal fluid (CSF). In the early stages, prions work as zombie proteins, damaging the brain without showing any loss of physical or mental abilities.
Rogue Proteins

Prion Proteins’ Superpowers

Misfolded proteins have the ability to replicate and spread disease by recruiting other normal proteins to misfold. One prion can turn into more than billions of prions over several years. Prion-proteins can move directly from cell to cell or travel through the blood or cerebral spinal fluid (CSF). 

In the early stages, prions work as Zombie Proteins, damaging the brain without showing any loss of physical or mental abilities.

Prion-Proteins’ Role In Alzheimer’s, Parkinson’s & Other Mixed Brain Diseases

In Alzheimer’s, misfolded proteins cause plaque and tangles.

In Parkinson’s, however, prion-proteins form Lewy Bodies.  Commonly observed under the microscope, plaque, tangles, and Lewy Bodies damage the brain in the following fashion:

  • Prions are soluble nanoparticles that spread disease by moving between connected nerve cells.

  • Prion-proteins appear to disrupt normal protein synthesis and degradation within nerve cells leading to cell death.

  • At high concentrations, misfolded proteins tend to form large insoluble aggregates easily detected under a microscope.

Alzheimer’s Prion Biomarkers

So far, scientists have discovered various types of misfolded proteins as biomarkers associated with Alzheimer’s and Parkinson’s.  It’s worth noting that some diseases may show more than one kind of Prion biomarker.

Most Alzheimer’s patients show two types of misfolded protein:

  • Abeta
  • Tau

Furthermore, among 20-40% of Alzheimer’s patients, we also find these two misfolded proteins:

  • Synuclein
  • TDP43

Parkinson’s Prion Biomarkers

In Parkinson’s patients’ brain, the single bad actor biomarker is the following misfolded protein:

  • Synuclein

Understanding how prions work in the early stages remains a top priority as we race to find a cure for Alzheimer’s, Parkinson’s, and other neurodegenerative diseases.

blog image - parkinson's diagnosis
Understanding how prions work in the early stages remains a top priority as we race to find a cure for neurodegenerative diseases.

What Causes Normal Proteins to Misfold?

Decades of research shows several vital factors that act as triggers to cause normal proteins to misfold. The main trigger-events include:

  1. Head Injury: such as traumatic head injuries.
  2. Genetics: Hereditary link to a family history of either Alzheimer’s or Parkinson’s.
  3. Environmental risks: exposure to infectious agents or toxic chemicals.

We're Cracking the Code On Misfolded Proteins

A research pioneer in misfolded proteins for nearly two decades, our team is confident in cracking the code on zombie proteins. Every day, our scientists are working to understand better the life cycle of misfolded proteins and how these silent-but-deadly-zombie-proteins function within the brain during the early stages. Our fundamental questions include the following:

  • How, where, and when normal proteins start to misfold, turning into zombie proteins
  • How are prion-proteins transported, both into the brain and within the brain?
  • How do these rogue proteins disrupt critical intracellular processes to cause cell death inside the brain?
  • What are the critical pathways leading to the loss of cognitive and motor control?
You can't be aware of everything. You'd fall down the stairs if you were aware of every intricate thing involved in going downstairs.
Alan Alda
Alan Alda