Researchers have mapped out precisely how Parkinson’s disease develops in animals in a study that could ultimately help the development of treatments for humans.
The research concluded that, in patients with Parkinson’s or other neurodegenerative disorders, the alpha-synuclein (a-syn) protein forms into clusters named Lewy bodies in the neurons. Irregular versions of the protein can induce normal a-syn to misfold and aggregate.
The study saw that when irregular a-syn proteins from mice with Parkinson’s disease and synthetic a-syn fibrils were injected into symptom-free mice with Parkinson’s, misfolded a-syn proteins multiplied along major central nervous system pathways before travelling to areas other than injection sites, showing that Lewy body formations can spread to healthy neurons.
Mutant proteins can get inside a neuron, recruit healthy a-syn protein in the cell and cause it to misfold, a process that is repeated along extensions to other neurons, leading to a dramatic accumulation of abnormal proteins.
Center for Neurodegenerative Disease Research director Dr Virginia Lee said, "Knowing this mechanism allows for possible immunotherapies to interrupt the chain reaction by stopping the mutant protein from spreading at the synapse.
"We think the spreading is via white-matter tracks through brain neural network connections. This study will open new opportunities for novel Parkinson’s disease therapies," added Lee.
The study was conducted at the Perelman School of Medicine at the University of Pennsylvania and published in the Journal of Experimental Medicine.
Image: A sample of substantia nigra in Parkinson’s disease, showing a neuron with a Lewy body. Photo: Werner CJ., Heyny-von Haussen R., Mall G., Wolf S.