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Arthur T Knackerbracket has found the following story:

All neurodegenerative diseases have a common thread: the appearance of protein clumps in the brain such as amyloid-beta plaques in Alzheimer's disease and alpha synuclein aggregates in Parkinson's. The root cause of this buildup has been hard to pinpoint, but Rockefeller scientists have identified a likely culprit that opens up a new avenue for developing treatments.

In a pair of studies carried out in flies and mice, the researchers discovered that the issue lies in the system that transports proteasomes, the molecular machinery that breaks down proteins, to specific locations within a cell.

[...] "This is the first study to find a mechanism by which the proteasomes are moved to nerve endings to do their job," says Hermann Steller, the Strang Professor at Rockefeller. "When this mechanism gets disrupted, there are severe consequences for the function and long-term survival of nerve cells."

Proteasomes are made in the cell body of a neuron and need to be transported over long distances to reach the nerve endings where the neuron connects with other cells--a journey of more than one meter in some cases. When proteasomes fail to reach these critical communication hubs, the cell descends into turmoil.

"Instead of being degraded, damaged proteins in these sites hang around long enough to interact with other binding partners, form aggregates, and disrupt cell function," Steller says. Over time, this causes degeneration of nerve fibers and ultimately cell death.

When Steller and his team began investigating the proteasome transportation system in fruit flies, they identified a protein called PI31, which plays a crucial role in loading the proteasomes onto the cellular components that ferry them around. In research published in Developmental Cell, they show that PI31 enhances binding and promotes movement of proteasomes with cellular motors. Without it, transport is halted. This is the case in both fly and mouse neurons, suggesting that the transport mechanism is common between many species.

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