Shared Synaptic Link Offers New Hope for Alzheimer's and Parkinson's
Okinawa Institute of Science and Technology Graduate University
Parkinson's and Alzheimer's diseases are two of the most prevalent neurodegenerative disorders, affecting millions worldwide. A groundbreaking study from the Okinawa Institute of Science and Technology (OIST) has revealed a shared molecular mechanism between these diseases, shedding light on the underlying synaptic dysfunctions that contribute to their symptoms.
The research, published in the Journal of Neuroscience, focuses on the disruption of brain cell communication through synapses by disease-related protein buildup. The scientists identified a pathway that interferes with synaptic vesicle recycling, a critical process for normal brain signaling. This discovery helps explain why a shared mechanism of synaptic dysfunction can lead to the distinct symptoms of both Alzheimer's and Parkinson's diseases.
Brain communication relies on neurotransmitters, which are chemical messengers produced within brain cells and stored in synaptic vesicles. These vesicles transport neurotransmitters to the synaptic cleft, where they release the chemicals into the space between cells, allowing for communication. For sustained signaling, vesicles must be retrieved, refilled, and reused.
The study uncovered a molecular cascade that disrupts the vesicle retrieval process, leading to abnormal brain function. When disease-related proteins accumulate in brain cells, they cause an overproduction of microtubules, which are essential for cell structure and function. This overproduction traps dynamin, a protein responsible for retrieving emptied vesicles from cell membranes, in the microtubules. As a result, the vesicle retrieval and recycling process slows down, hindering brain cell communication.
Therapeutic Implications
The authors have identified several potential drug discovery targets by revealing this shared mechanism. Professor Emeritus Tomoyuki Takahashi from OIST suggests preventing disease-related protein accumulation, stopping microtubule overproduction, or disrupting microtubule-dynamin bindings as potential therapeutic strategies. These targets are common across Parkinson's and Alzheimer's diseases.
This research builds upon the team's previous work, including studies on microtubules in Parkinson's disease and the interaction between dynamin and microtubules in Alzheimer's disease. In 2024, they discovered a peptide that reversed Alzheimer's symptoms in mice, and they hypothesize that this same molecule could potentially alleviate Parkinson's symptoms as well.
The study's findings offer a promising avenue for developing new treatments to mitigate the impact of these diseases on patients, families, and society.
