How toxic forms of alpha-synuclein get into these dopamine-producing brain cells

Armin Bayati
McGill University
Graduate Student Award
$20,000 over 2 years
Pathological a-synuclein: endocytosis and internalization mechanism

Brain cells don’t just let any proteins through their membranes, but unfortunately, they make an exception for a toxic form of protein called alpha-synuclein that’s at the heart of Parkinson’s disease.

Researchers know misshapen or mutated forms of alpha-synuclein form clumps and ultimately kill brain cells that produce dopamine. Dopamine is the signaling chemical that communicates with other brain cells to control movement. When dopamine-generating brain cells die, Parkinson’s disease occurs.

What researchers don’t yet know is how toxic forms of alpha-synuclein get into these dopamine-producing brain cells, and how they spread.

At McGill University, PhD student Armin Bayati is taking a close, second-by-second look as this process happens, and then how this unwelcome visitor spreads to other cells.

“What I want to know is, where is it (alpha-synuclein) going as it enters the cell, and what structures or receptors on the cell is it using to get in,” says Bayati.

Bayati adds fluorescent alpha-synuclein to cultures containing cell lines. He then uses imaging equipment to track the alpha-synuclein’s journey and spot other proteins or group of proteins helping it along its way.

“Once we find that one protein or group of proteins that let alpha-synuclein in (to cells), then the sky’s the limit. We can stop it from ever spreading.”

He’s already discovered that in less than two minutes, alpha-synuclein enters directly into the compartments of cells called lysosomes that break down proteins and sugars.

“We’ve seen this entry at a very fast rate that’s not normal for any other protein,” Bayati says.

If Bayati can find additional proteins or groups of proteins helping toxic alpha-synuclein enter brain cells so quickly, he’ll have identified an excellent

target for drug therapy that could stop the progression of Parkinson’s disease, or even prevent it.

“Once we find that one protein or group of proteins that let alpha-synuclein in, then the sky’s the limit. We can stop it from ever spreading,” Bayati says.

He’ll also explore how the toxic alpha-synucleins spread from cell to cell.

Bayati grew up surrounded by science: his mother is a pharmacist and his uncles are doctors. He chose neuroscience because he is fascinated by what he learns by imaging cells, and he loves the dynamic nature of his work.

“The experiments you are looking at, the findings, the collaboration, are never the same. It’s my attempt at having an exciting life,” he says.