(CN) — Researchers have made progress on a potentially promising new early treatment for Alzheimer's disease and other neurodegenerative diseases such as Parkinson's and amyotrophic lateral sclerosis, or ALS.
The treatment relies on autophagy, the process by which your body repairs cells and clears out damaged or dysfunctional components within in cells.
"In a lot of neurodegenerative diseases, one of the most fundamental problems is defects in autophagy, when the cell repair system fails," said Scott Selleck, professor of biochemistry and molecular biology at the Penn State Eberly College of Science and leader of the research team. "We found a mechanism for turning up the gain on that process, to give cells a greater capacity to repair damage."
According to the Alzheimer's Association, nearly 7 million Americans over the age of 65 are living with the disease. There is no consensus on its root cause. Scientists have known for some time that a class of sugar-modified proteins, heparan sulfate proteoglycans, are involved in the disorder, but their contribution to disease mechanisms is poorly understood. Heparan sulfate is a linear chain of sugars, attached to proteins on cell surfaces an in the spaces between cells.
Researchers have also known, for years, how to use genetic engineering to inhibit an enzyme responsible for producing heparan sulfate, a chain of sugar molecules.
In a paper published Tuesday in the journal "iScience," Selleck and his team show that inhibiting heparan sulfate synthesis with genetic tools activates the autophagy process to indeed boost cell repair.
The paper, Selleck said, "connects the dots" between earlier works and theories and shines some light about the relationship between some recent human genetics findings of early onset Alzheimer's and those sugar chains, heparan sulfate.
The Food and Drug Administration recently approved two drugs for treating Alzheimer's — they slow the progression of the disease to a degree by blocking accumulation of proteins, called amyloid, that are prominent in late stages of the disease. Selleck's approach, meanwhile, focuses on the cell abnormalities found in the earliest stages of neurodegenerative diseases.
"We're seeing effects on cell processes that are fundamental to neurodegenerative diseases," Selleck said. "That, to me, is vital — we're trying to tackle something at the fundamental base of the problem."
In their study, Selleck and his team analyzed human cell lines and mouse brain cells to prove that inhibiting heparan sulfate-modified proteins boosts autophagy. Doing so also improved the function of mitochondria, which are responsible for energy production in the cell, and reduced build-up of lipids, or fatty compounds, inside cells.
He and his colleagues also studied the brains of fruit flies, which have one peculiar thing in common with humans: Both are vulnerable to a mutation of a gene called presenilin, that causes early onset of Alzheimer's in people and neuron loss in fruit flies. Humans with mutations in a presenilin gene will get Alzheimer's at around the age of 45 years old. Selleck said that he and his team were able to show that modestly inhibiting heparan sulfate synthesis "rescues those dying neurons in our model system."
All in all, Selleck said, the paper should be seen as an encouraging sign in the fight against Alzheimer's, Parkinson's and ALS.
"I think in 10 years, hopefully sooner, we’ll have a lot better tools to help patients," Selleck said. "We've been able to show that a little inhibition of heparan sulfate synthesis, like that which could be readily achieved with a drug, produces really good effects.”
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