New Breakthrough: Blocking Protein Interaction to Halt Parkinson’s Spread
Researchers have discovered that a cell surface protein called Aplp1 plays a role in spreading Parkinson’s disease-causing agents between brain cells. This interaction with another protein, Lag3, has led to an FDA-approved cancer treatment blocking this spread in mice, suggesting existing potential treatments.
An international team of scientists will explore how these proteins facilitate harmful alpha-synuclein protein entry into brain cells. Understanding the Aplp1-Lag3 interaction provides new insights into Parkinson’s progression, offering avenues for targeted treatments to slow disease advancement.
Parkinson’s affects over 85,000 people globally, ranking second after Alzheimer’s in neurodegenerative diseases. Symptoms like tremors, stiffness, and balance issues arise from neuron death in the brain’s substantia nigra, affecting dopamine production crucial for motor control. The disease involves abnormal protein clumps, mainly comprised of misfolded alpha-synucleins transferring between neurons.
Previous mouse studies showed Lag3 binding to alpha-synuclein, spreading Parkinson’s pathology. Removing Lag3 hindered this process but did not entirely prevent it, indicating involvement of other proteins.
Tests on genetically modified mice lacking Aplp1, Lag3, or both revealed their independent roles in facilitating alpha-synuclein uptake by brain cells, with combined deletion significantly reducing uptake. Deleting both proteins stabilized brain health when almost all harmful alpha-synuclein was absorbed by healthy cells.
Testing the melanoma drug containing Lag3 antibodies (nivolumab/relatlimab) on normal mice inhibited Aplp1-Lag3 interaction, nearly halting disease-causing alpha-synuclein clump formation in neurons.
“The anti-Lag3 antibody effectively halted further alpha-synuclein seed diffusion in mouse models, showing better efficacy than Lag3 depletion alone due to Aplp1’s close association,” stated Ted Dawson, a neuroscientist at Johns Hopkins University.
Future research will involve testing Lag3 antibodies in mouse models of Parkinson’s and Alzheimer’s, targeting Lag3 as a promising approach.
Source: New Breakthrough: Blocking Protein Interaction to Halt Parkinson’s Spread
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