Neuronal activity causes a use-dependent decline in protein function. However, how this is coupled with local quality control mechanisms is still being determined.
A gene linked to a higher risk of Parkinson’s disease may also have a role in the accumulation of cell debris in the brain, according to the University of Queensland researchers. They found that Parkinson’s disease -linked mutation in a gene called Endophilin A1 blocks the autophagy process by which the body and the brain recycle cell waste.
Without Autophagy, toxic debris builds up, and neurons die – known hallmarks of Parkinson’s Disease.
Dr. Adekunle Bademosi from The Queensland Brain Institute said, “We knew we could induce autophagy in cells by starving them of amino acids, and the subsequent breakdown of debris tells a protein called EndoA to approach the cell membrane and begin the recycling process.”
“Now we’ve also seen that regular signals between neurons in the brain start EndoA-induced autophagy when the electric impulses trigger the release of proteins or neurotransmitters at synapses.”
“Unfortunately, when the Endophilin A1 gene is affected in Parkinson’s, the protein EndoA becomes insensitive to this trigger at the synapse, and the debris that should be thrown out for recycling builds up instead.”
“Current Parkinson’s treatments focus on clearing out the build-ups and replacing what is lost when too many neurons die. It may be time to shift the treatment focus to autophagy as the mechanism underlying these disease hallmarks.”
“Exploring the use of compounds that induce or inhibit autophagy could pave the way for new, more effective Parkinson’s drugs.”
- Adekunle T. Bademosi et al. EndophilinA-dependent coupling between activity-induced calcium influx and synaptic autophagy is disrupted by a Parkinson-risk mutation. Neuron. DOI: 10.1016/j.neuron.2023.02.001