An abstract image representing shared mechanisms. Two silhouettes are featured back-to-back with joint cog wheels in bright colours across their heads, representing the shared synaptic mechanism. A brightly coloured background of yellow, blue, green red and orange evokes positivity with the news that this shared mechanism may inform potential treatment options. Credit: Kaori Serakaki/ OIST. CC BY.

The discovery of a shared synaptic mechanism for Alzheimer’s and Parkinson’s disease could unlocked new treatment possibilities.

The new study has revealed a common mechanism affecting brain signalling, identifying a shared cause for neurodegenerative disease symptoms.

Parkinson’s and Alzheimer’s diseases are the two most common neurodegenerative disorders, affecting millions of people worldwide.

New research from the Okinawa Institute of Science and Technology (OIST) suggests a shared molecular cascade between the two diseaseswhich causes synaptic dysfunctions, advancing our understanding of how their symptoms are produced. 

The researchers investigated how brain cell communication across synapses is disrupted by disease-related protein buildup.

They found a pathway that interferes with synaptic vesicle recycling, which is crucial for normal brain signalling.

First author Dr Dimitar Dimitrov of OIST’s Synapse Biology Unit said: “Synapses are communication hubs in the brain involved in different neuronal circuits controlling different functions.

“Therefore, protein accumulation in synapses of one neuronal circuit may impact memory, while in another it may impair motor control.

“This helps to explain how a shared mechanism of synaptic dysfunction can lead to the distinct symptoms of both Alzheimer’s and Parkinson’s diseases.” 

Brain communication and the importance of vesicles 

Brains rely on neurotransmitters to send signals between cells.

These chemical messengers are produced within brain cells and stored and transported in small membranous packets called synaptic vesicles.

Vesicles move and fuse with cell membranes, releasing the neurotransmitters into the synaptic cleft, where they diffuse to reach receptors on nearby cells.

For sustained signalling, vesicles must be retrieved from the membrane, refilled with neurotransmitters, and then reused.  

In this study, the researchers identified a molecular cascade which interrupts the vesicle retrieval process, disrupting normal brain function.  

Dimitrov said: “When disease-related proteins accumulate in brain cells, they cause over-production of protein filaments called microtubules, which are normally essential in cell structure and function.

“When over-produced, these microtubules trap a protein called dynamin, which is responsible for the retrieval of emptied vesicles from cell membranes, playing a crucial role in vesicle recycling.

“With less dynamin, vesicle retrieval and recycling slow, thereby interrupting signalling and communication between brain cells.” 

Therapeutic implications for Alzheimer’s and Parkinson’s diseases 

By revealing this new shared mechanism, the authors identify several different steps which could be drug discovery targets.

OIST Professor Emeritus Tomoyuki Takahashi said: “Preventing disease-related protein accumulation, stopping microtubule over-production, or disrupting microtubule-dynamin bindings – our new mechanism identifies three potential therapeutic targets common across Parkinson’s and Alzheimer’s disease.

“Research like this is important to develop new treatments that ease the impact of these diseases on patients, families, and society as a whole.” 

This study builds on a long history of neuroscience research by the team, who previously published research on the involvement of microtubules in Parkinson’s disease and of dynamin-microtubules interaction in Alzheimer’s disease. In2024, they reported a peptide which reversed the symptoms of Alzheimer’s disease in mice. 

Based on their latest findings, the researchers believe this same molecule could potentially be used to relieve Parkinson’s disease too.

The study is published in the Journal of Neuroscience.