Parkinson's Protein Mutation Eases Cellular Traffic

Researchers find a way to reduce traffic jams and restore flow by altering how two Parkinson's-related proteins interact.

Feb. 5, 2026 at 11:31pm

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Researchers at the University at Buffalo have identified a way to reduce the traffic jams caused by the buildup of the Parkinson's-related protein alpha-synuclein. By increasing levels of a specific mutant form of the LRRK2 protein, they found that it can limit alpha-synuclein's ability to bind to cargo and disrupt axonal transport within neurons.

Why it matters

This finding suggests a functional link between two of the key genes known to cause familial Parkinson's disease, providing a clearer picture of how the disease may start at the earliest stages. Understanding these protein interactions could lead to new therapeutic approaches for Parkinson's.

The details

The researchers found that a mutation in the WD40 domain of the LRRK2 protein can suppress its ability to interact with alpha-synuclein, easing the traffic jams caused by excess alpha-synuclein binding to cargo within the neuron's axons. However, this LRRK2 mutation did not affect neuronal cell death or Lewy body formation, which are other hallmarks of Parkinson's disease.

  • The study was published last month in the journal Frontiers.

The players

Shermali Gunawardena

The corresponding author of the study and an associate professor of biological sciences in the UB College of Arts and Sciences.

LRRK2

A Parkinson's-related protein that, when mutated, can interact with alpha-synuclein in a way that reduces traffic jams in neurons.

Alpha-synuclein

A protein that, when misfolded, can build up and form Lewy bodies, a hallmark of Parkinson's disease. High levels of alpha-synuclein can also disrupt the transport of proteins and cargo within neurons.

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What they’re saying

“This finding suggests that alpha-synuclein and LRRK2 proteins must act together — and be in the right balance — for axonal transport to be disrupted.”

— Shermali Gunawardena, Associate professor of biological sciences (Frontiers)

“A mutation doesn't necessarily kill a protein's function. It can exaggerate it, suppress it, or lead to an entirely new function. It can be complicated to untangle, but in this case the results suggest the WD40 mutation can suppress LRRK2's ability to interact with alpha-synuclein, perhaps within membranes.”

— Shermali Gunawardena, Associate professor of biological sciences (Frontiers)

What’s next

The researchers say it is still unclear whether the LRRK2 mutations and improved axonal transport have any effect on the later formation of Lewy bodies, another key hallmark of Parkinson's disease.

The takeaway

By finding a functional link between two of the key genes known to cause familial Parkinson's disease, this study provides a clearer picture of how the disease may start at the earliest stages, which could lead to new therapeutic approaches targeting the interaction between alpha-synuclein and LRRK2.