Researchers have found that a protein known to cause epilepsy in infants does so by a trigger clumping the alpha-synuclein protein — a process causing brain toxicity that is more commonly linked to Parkinson’s disease.
The study, “Munc18-1 is a molecular chaperone for α-synuclein, controlling its self-replicating aggregation,” published in the Journal of Cell Biology, advances the understanding of this serious conditions in newborns, and may lead to the development of new types of treatments for the disease.
Munc18-1 is a protein belonging to the array of molecules that control the release of neurotransmitters — the molecules acting as chemical messengers, allowing a signal to pass from one nerve to the next.
Mutations in the gene coding for Munc18-1 lead to developmental problems and the rare type of epilepsy known as infantile epileptic encephalopathy (EIEE). Only about half of babies that are diagnosed with the condition survive.
“We already knew that mutations in the molecule known as Munc18-1 triggered this rare epileptic syndrome, but this groundbreaking study, led by PhD student Ye Jin Chai, has isolated the exact process,” senior author Fred Meunier, a professor from the Clem Jones Centre for Ageing Dementia Research at Australia’s University of Queensland, said in a news release.
The research team discovered that when Munc18-1 was mutated, the protein alpha-synuclein — normally present throughout the brain — started aggregating into clumps, much like researchers observe in the brains of patients with Parkinson’s disease and related conditions. These clumps are toxic to neurons, causing the degeneration seen in these conditions.
This is not the first time that alpha-synuclein, a protein mainly studied in the context of neurodegeneration, is linked to epilepsy. A study of patients with epilepsy not responding to treatment found elevated levels of the protein in the cerebrospinal fluid, and another study found that the protein expression in brains of patients with mesial temporal lobe epilepsy differ from that of healthy people.
However, researchers have never before observed the aggregation of the protein — a process so far mainly linked to neurodegeneration — in an epileptic state.
“This is the first time that a communal mode of action has been found for an epileptic syndrome and neurodegeneration,” said Dr. Emma Sierecki from the University of New South Wales, a co-author on the study who is focusing her research on protein aggregation linked to neurodegenerative diseases.