Following a breakthrough in Alzheimer’s research, National Yang Ming Chiao Tung University (NYCU) scientists have now made another leap forward in studying neurodegenerative diseases—this time focusing on Parkinson’s disease.
A research team led by Dr. Margaret S. Ho, Associate Professor at NYCU’s Institute of Neuroscience, has identified a novel cellular pathway that clears toxic proteins from the brain, preventing the death of dopamine-producing neurons, a hallmark of Parkinson’s disease. The study, titled “Drosophila aux orchestrates the phosphorylation-dependent assembly of the lysosomal V-ATPase in glia and contributes to SNCA/α-synuclein degradation,” was recently published in the prestigious international journal Autophagy.
Toxic Protein Buildup: A Shared Culprit in Parkinson’s and Alzheimer’s
Like Alzheimer’s disease, Parkinson’s is characterized by the abnormal accumulation of toxic proteins. Dr. Ho’s team discovered that a gene known as GAK (in mice) or aux (in fruit flies) plays a critical role in regulating lysosomal acidification, a process essential for breaking down these proteins, especially alpha-synuclein (α-synuclein), the primary toxic agent in Parkinson’s.
Their findings show that this gene is predominantly expressed in glial cells, which regulate lysosomal pH and enzyme activity. Without this gene, the lysosomes lose their acidic environment, preventing them from degrading harmful proteins. As a result, these proteins accumulate and severely damage brain cells.
Animal Studies Reveal Striking Similarities to Human Parkinson’s
Experimental models confirmed the mechanism. Fruit flies lacking the aux gene showed impaired motor abilities and shortened lifespans, while mice without the GAK gene exhibited Parkinson’s-like symptoms such as unsteady gait and slowed movement. These findings closely mirror the degenerative symptoms seen in human patients.
A Molecular “Valve” for the Brain’s Waste Disposal System
Dr. Ho emphasized that her team had already flagged the GAK/aux gene as a potential player in Parkinson’s disease as early as 2017. This new study goes a step further, identifying the gene as a molecular valve for lysosomal acidification. By maintaining the proper environment inside lysosomes, this valve controls the brain’s ability to break down and clear toxic proteins, effectively powering the cell’s waste disposal system.
“When this switch fails,” Dr. Ho explained, “the entire system shuts down.”
A New Hope for Parkinson’s Treatment
“This discovery is significant,” said Dr. Ho. “It tells us that if we can reactivate this molecular switch, glial cells can once again clear toxic proteins. This opens the door to a promising new therapeutic target for Parkinson’s disease.”
As global populations continue to age, the urgency for innovative treatments for neurodegenerative diseases has never been higher. NYCU’s discovery not only advances our understanding of Parkinson’s but also brings renewed hope for effective therapies shortly.
