Discovering Ways to Protect the Brain from Neurodegeneration

Mitochondria are labelled bright green against a black background. Their shapes are oval with compartments inside.

Credit: stock image

Parkinson’s disease is a neurodegenerative disorder characterized by abnormal accumulation of an intrinsically disordered protein called alpha-synuclein (αSyn) in neurons. Studies have suggested that upon accumulation, αSyn enters mitochondria—intracellular organelles that power the cell—and disrupts energy production. However, researchers were unsure exactly how αSyn enters mitochondria.

The Bezrukov Lab studies proteins that span the mitochondrial outer membrane and serve as transport channels enabling regulation of the fluxes of ions, metabolites, and proteins entering and exiting mitochondria. One of these channels is called the voltage-dependent anion channel (VDAC).

In a study led by Dr. Tatiana K. Rostovtseva, researchers in the lab identified VDAC as a pathway for αSyn entering mitochondria. The study shows that in a cell model of Parkinson’s disease, αSyn enters exclusively through VDAC and disrupts mitochondrial functions. Their findings also help explain why an experimental drug called olesoxime is neuroprotective—the drug prevents translocation of αSyn through VDAC.

Overall, the work identifies VDAC as a potential new therapeutic target for Parkinson’s disease and possibly other types of neurodegenerative diseases. The findings align with a model where VDAC serves as the main docking site for misfolded proteins in neurons, such as amyloid β in Alzheimer’s disease. However, more research is needed to evaluate these innovative ideas.

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