In a breakthrough finding, researchers have discovered to successfully switch off a key route for nerve fibre failure in debilitating neurodegenerative diseases such as Parkinson’s, glaucoma, and traumatic brain injury.
The study led by Institute for Glycomics and Disarm therapeutics at Griffith University explains the structural processes behind activation and inhibition of SARM1 – a major molecule for the damage of nerve fibers.
The understanding of action of SARM1 is important to help to treat several neurodegenerative conditions, which is a trigger for nerve fiber degeneration.
Importantly, the study demonstrates the molecular interactions that can switch SARM1 on and off. This provides a clear path for the design of new drug therapeutics.
Meanwhile, for neurodegenerative disorders such as Parkinson’s, peripheral neuropathy, traumatic brain injury, and glaucoma, the damage of nerve fibers activates SARM1.
This triggers a series of molecular processes that lead to self-destruction of axon of the nerve cell – the cable that transmits electric impulse away from one nerve cell to the other.
Anatomically, the axon is several times thinner than a human hair, but is up to a meter in length. It stretches from brain to the spinal cord, and its destruction can lead to serious dysfunction.
The SARM1 protein works like a sensor and responds to the environment. The molecule switches on when the levels of nicotinamide mononucleotide, which is a small activator molecule increases. The activator molecule attaches to the larger SARM1 protein like a key in a lock thereby initiating the process that lead to the breakdown of nerve fibers. SARM1 when unlocked is able to disintegrate another key molecule called nicotinamide adenine dinucleotide, which provides energy for nerve fibers to function and continue to live.