Dementia and the Strange Case of the Misfolded Protein

Health Professional

Some images are hard to shake off. During the late 1990s I vividly recall driving past burning heaps of dead cattle for mile after mile; the scene was medieval. The cause of this carnage was a disease that quickly became known as 'mad cow' a fatal and degenerative disease of the nervous system that caused cattle to behave strangely. The disease was eventually tracked down to a particular kind of protein that effectively clogged up brain tissue.

When it was discovered that mad cow disease was transmissible to humans the spotlight fell on a particular kind of protein called a prion. Prions are unique in the sense they can reproduce on their own and become infectious. To date the Centers for Disease Control and Prevention (CDC) identify five human prion diseases:

Creutzfeld-Jakob Disease (CJD)

Variant Creutzfeld-Jakob Disease (vCJD)

Gerstmann-Straussler-Scheinker Syndrome

Fatal Familial Insomnia

Kuru

Professor Corinne Lasmezas of The Scripps Research Institute, has spent years investigating prion diseases. In a report by Jon Hamilton for NPR, Dr. Lasmazas makes the point that many common features exist between prion diseases and other diseases like Alzheimer's, Parkinson's and amyotrophic lateral sclerosis. In mad cow (bovine spongiform encephalopathy) misfolded proteins spread by causing normal cells next to them to change shape. InAlzheimer's, a similar misfolding process is seen in proteins called beta-amyloid and tau. In both cases when misfolded proteins reach critical mass they start a chain reaction, eventually destroying the brain.

The race is on to find ways of either neutralizing misfolded proteins or finding ways to protect normal brain cells from their effects. The destructive mechanism prion proteins seem to use is to kill healthy neurons by depleting a molecule called NAD. Some success has been found in experiments that replenish NAD, the effect of which seems to completely protect against misfolded proteins.

A problem yet to be solved is what causes proteins to change their shape and become misfolded in the first place. Understanding the causes for neurodegenerative diseases like Alzheimer's has some way to go. Opening up new mechanisms for understanding the process is helpful but, as yet, it remains unclear as to the potential benefits.

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