Researchers Discover Potential Therapy for Parkinson’s Disease by Targeting Cell Surface Protein
Recent research has uncovered a significant breakthrough in understanding the progression of Parkinson’s disease. Scientists have identified how a cell surface protein called Aplp1 plays a crucial role in facilitating the spread of alpha-synuclein protein clumps, responsible for the development of Parkinson’s disease, from cell to cell in the brain. This discovery opens up new possibilities for potential therapeutic interventions.
The study, detailed in a recent paper by an international team of researchers, highlights the interaction between Aplp1 and Lag3, another protein that binds to alpha-synuclein. By targeting Lag3 with an FDA-approved cancer drug, researchers were able to block the spread of harmful alpha-synuclein in mice, suggesting a promising avenue for treatment.
Neuroscientist Xiaobo Mao from Johns Hopkins University emphasized the significance of this finding, stating that understanding the role of Aplp1 and Lag3 in Parkinson’s disease progression provides a new perspective on potential therapeutic strategies. By targeting this interaction with drugs, researchers aim to slow down the progression of not only Parkinson’s disease but also other neurodegenerative disorders.
Parkinson’s disease affects more than 8.5 million people globally, making it the second most common neurodegenerative disease after Alzheimer’s. Characterized by symptoms such as tremors, stiffness, balance problems, speech difficulties, and cognitive impairments, Parkinson’s disease poses significant challenges for patients. Currently, there is no cure for the disease, and patients may eventually experience difficulties with mobility and communication.
The underlying cause of Parkinson’s disease lies in the death or dysfunction of dopamine-producing neurons in the substantia nigra region of the brain. This neuronal damage is believed to be triggered by the accumulation of Lewy bodies, abnormal protein clumps primarily composed of misfolded alpha-synuclein that propagate between neurons.
Alpha-synuclein, a protein critical for neuronal communication, becomes problematic when it misfolds and aggregates, leading to neurodegenerative processes. However, determining whether this protein aggregation is a cause or a consequence of Parkinson’s disease remains a complex challenge.
Past studies on mouse models have shown that Lag3 interacts with alpha-synuclein proteins, contributing to the spread of Parkinson’s disease pathology in neurons. While targeting Lag3 alone can impede this process, researchers discovered that Aplp1 also plays a significant role in facilitating the uptake of misfolded alpha-synuclein by brain cells.
By conducting experiments on genetically modified mice lacking either Aplp1, Lag3, or both proteins, scientists demonstrated that Aplp1 and Lag3 independently promote the absorption of harmful alpha-synuclein. However, when both proteins are absent, the uptake of alpha-synuclein by healthy brain cells is significantly reduced, indicating a synergistic effect.
Furthermore, administering a cancer drug containing a Lag3 antibody to normal mice effectively disrupted the interaction between Aplp1 and Lag3, thereby preventing the formation of disease-causing alpha-synuclein clumps in neurons. This promising result suggests that targeting these proteins with specific drugs could offer a viable therapeutic approach for Parkinson’s disease.
Future research will focus on testing the Lag3 antibody in mouse models of Parkinson’s disease and Alzheimer’s, where Lag3 has also been identified as a potential therapeutic target. The findings of this study have been published in Nature Communications, paving the way for innovative treatment strategies for neurodegenerative diseases.
An earlier version of this article was published in June 2024.
