Yeast Contra Parkinson’s

Photo: One picture with few, another with many red points

Red staining makes the increased
survival of dopamine-producing
neurons visible in the rat brain with
Hsp104 (right bottom) and that
without (right top); © J. Shorter

So far, no treatments are available that fundamentally alter the course of Parkinson's disease. By introducing the yeast protein Hsp104 into animal models of Parkinson’s disease, researchers prevented protein clumping that leads to nerve cell death characteristic of the disorder.

“Yeast express a protein called Hsp104, which is able to reverse protein aggregation,” says James Shorter, PhD, Assistant Professor of Biochemistry and Biophysics and one of the authors. “However, for reasons that are unclear, Hsp104 is not found in mammals. We wondered if introducing Hsp104 into mammals could help with diseases connected with protein aggregation.”

Clinicians do not fully understand the process and cause of Parkinson’s disease. However, researchers believe that a protein called alpha-synuclein misfolds and clumps in many forms of the disease, and that this process is intimately tied to the selective death of dopamine-producing neurons that results in Parkinson’s disease.

In this study, researchers found that Hsp104 could partially reverse alpha-synuclein aggregation in test-tube experiments. Remarkably, rats expressing Hsp104 showed lower levels of alpha-synuclein aggregation and alpha-synuclein-induced toxicity of neurons. This result is significant because the rat model used recreates the selective loss of dopamine-producing nerve cells in the region of the brain affected in Parkinson’s disease, say the investigators.

“This study represents an important preliminary step,” says Shorter. “One thing we’d like to do next is to treat an animal model which already has considerable quantities of alpha-synuclein aggregates to see if Hsp104 can actually reverse the process in the rat brain.”; Source: University of Pennsylvania School of Medicine