AsianScientist (Jun. 13, 2017) – In a study published in the Journal of Neuroscience, researchers have identified how a protein called alpha-synuclein could cause Parkinson’s disease.
Parkinson’s disease is a debilitating neurological illness that affects approximately ten million people worldwide. It is marked by a progressive decline in physical function, the most iconic being uncontrollable tremors, and involves the malfunction and eventual death of nerve cells located in the brain. There is no cure for this disease, and researchers have struggled for years to fully understand its cause.
In the 1990s, the field of Parkinson’s research took a great leap forward when an overabundance of the protein alpha-synuclein was linked to disease development. This protein, a mysterious inhabitant of the brain, is found mainly at the end of neurons in what is called the nerve terminal. However, attempts to precisely identify its role in Parkinson’s since the link was discovered have been unsuccessful, until now.
In the present study, a team of researchers at the Okinawa Institute of Science and Technology Graduate University (OIST) have found that too much alpha-synuclein hinders a key step involved in the transmission of neuronal signals: vesicle endocytosis at the nerve terminal.
During neurotransmission, the electrical signal that arrives at a nerve terminal triggers the release of chemical messengers called neurotransmitters from packages called vesicles into the space between neurons. The neurotransmitters are then caught by receptors on an adjacent neuron and the signal is passed along for further transmission.
Meanwhile, the empty vesicles are recycled back into the nerve terminal through a process called endocytosis. The OIST team found that an overabundance of alpha-synuclein targets this process, thereby affecting proper neurotransmission.
“If you inhibit [endocytosis in the nerve terminal], then the vesicle recycling becomes slower and the supply of the vesicles is inhibited,” explained Professor Tomoyuki Takahashi from the Cellular and Molecular Synaptic Function Unit. “If you are using the vesicles mildly, this is okay, but if you start to use them heavily, then it becomes a problem.”
For example, vesicles are heavily used during high-frequency transmission, which is important for processes such as sensory perception, generating memories and motor control. The OIST researchers found that when endocytosis is inhibited, high-frequency transmission breaks down much more quickly than it would under normal circumstances.
Further investigation showed that alpha-synuclein inhibits endocytosis by assembling too many microtubules.
“Microtubule is a structure protein,” Takahashi explained. “It’s like a pillar of a house.”
Too much alpha-synuclein in the nerve terminal causes microtubules to over-assemble and somehow get in the way of endocytosis, a situation akin to having too many pillars in a house and in all the wrong places.
The researchers believe that this inhibitory process caused by an overabundance of alpha-synuclein is what occurs in the early stages of Parkinson’s disease, before morphological changes such as the loss of function and death of neurons begins.
Source: Okinawa Institute of Science and Technology Graduate University.
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