Neuronal activity causes a use-dependent decline in protein function. However, how this is linked to local quality control mechanisms is still being determined.
A gene linked to a higher risk of Parkinson’s disease may also play a role in the accumulation of cell debris in the brain, according to the University of Queensland researchers. They found that the mutation in a gene called Endophilin A1 linked to Parkinson’s disease blocks the autophagy process by which the body and brain recycle cell waste.
Without autophagy, toxic waste 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 start the recycling process.”
“Now we have also seen that regular signals between neurons in the brain initiate EndoA-induced autophagy when the electrical impulses trigger the release of proteins or neurotransmitters at synapses.”
“Unfortunately, when the Endophilin A1 gene is compromised in Parkinson’s, the protein EndoA becomes desensitized to this trigger at the synapse, and instead it accumulates waste that should be disposed of for recycling.”
“Current Parkinson’s treatments focus on clearing up the buildup and replacing what is lost when too many neurons die. It may be time to shift the focus of treatment to autophagy as the mechanism underlying these disease features.”
“Exploring the use of compounds that induce or inhibit autophagy could pave the way for new, more effective Parkinson’s drugs.”
Magazine reference:
- Adekunle T. Bademosi et al. EndophilinA-dependent coupling between activity-induced calcium influx and synaptic autophagy is disrupted by a Parkinson’s risk mutation. neuron. DOI: 10.1016/j.neuron.2023.02.001
