How Toxic Proteins Kill Brain Cells and How to Stop it

toxic proteins kill brain cells

A discovery detailing how misfolded toxic proteins kill brain cells might lead to new treatments for neurodegenerative diseases like Alzheimer’s, Parkinson’s and prion diseases.

Neurodegenerative diseases are diseases that affects and kills neurons in the brain. The death of these brain cells causes a loss of function that varies with the disease sometimes leading to death. Some neurodegenerative diseases, like prion diseases or Alzheimer’s, are caused by misfolded proteins that causes damage. New research from the Scripps Research Institute have discovered how misfolded toxic proteins kill brain cells and how to prevent it. A discovery that might lead to new treatments for many diseases caused by misfolded proteins.

How toxic proteins Kill Brain Cells and How to Stop it

The study was published in the journal Brain.

“Our study reveals a novel mechanism of neuronal death involved in a neurodegenerative protein-misfolding disease,” said Corinne Lasmézas, a TSRI professor who led the study. “Importantly, the death of these cells is preventable. In our study, ailing neurons in culture and in an animal model were completely rescued by treatment, despite the continued presence of the toxic misfolded protein. This work suggests treatment strategies for prion diseases—and possibly other protein misfolding diseases such as Alzheimer’s.”

In the study researchers used a model involving a misfolded form of a prion disease protein called TPrP. This was a model researchers had previously developed to observe how toxic proteins like TPrP causes neurons to die. Toxic protein build-up in brain tissue is what causes damage in many brain diseases including Alzheimer’s, Parkinson’s and prion diseases.

Researchers found that TPrP killed neurons by depleting a metabolite called NAD+, a coenzyme involved in energy production and maintaining a state of cell equilibrium. Not only did they find how the protein caused damage, they were also able to reverse it.

By infusing NAD+ into neurons as long as three days after they were damaged by TPrP rescued neurons that were doomed to destruction. In mice this worked both when NAD+ were injected directly into the brain and when administering it through the Nose.

[pullquote]“Our study shows for the first time that a failure of NAD+ metabolism is the cause of neuronal loss following exposure to a misfolded protein,” Lasmézas said.[/pullquote]

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