Proteins found on the surface of and between animal cells could be a target for drugs aimed at stopping Alzheimer’s disease in its early stages, a new study suggests.
These proteins – heparan sulfate-modified proteoglycans (HSPGs) – are involved in the regulation of cell growth and the interaction of cells with their environment, and have already been studied in relation to neurodegenerative diseases.
These links encouraged the American team behind the study, led by researchers from Pennsylvania State University, to investigate further.
The role of these proteins in the proper functioning of the body, including autophagy (the cellular repair process that removes waste, disrupted in some types of dementia), makes them worthy of further investigation, the authors say.
“Treatment strategies for Alzheimer’s disease have so far focused largely on the pathological changes that occur in the later stages of the disease,” says molecular biologist Scott Selleck of Pennsylvania State University.
“Drugs that address the earliest cellular deficits could provide important tools to stop or reverse the disease process.”
In tests on genetically modified fruit flies, mouse brain cells, and tissues derived from human cells, the researchers observed disruption of key processes in which HSPGs are involved. In addition to autophagy, these processes include cellular energy production and the accumulation of fatty compounds called lipids.
When the team made some changes to how HSPGs worked, some of the damage associated with dementia was reversed. Cells were able to repair themselves better and neuron death was stopped.
Additionally, when human cells were prevented from producing heparan sulfate chains, it affected more than half of the approximately 70 genes linked to later stages of Alzheimer’s disease. It is thought that HSPGs may play a role at different stages of disease progression.
This research is still in its early stages, and these links are only just beginning to be identified. Eventually, much more research will be needed to develop drugs that interact with HSPGs to treat Alzheimer’s disease. However, it appears to be another promising avenue for experts to explore.
“Targeting the enzymes that produce heparan sulfate could provide a way to block neurodegeneration in humans,” Selleck says.
It is estimated that more than 55 million people suffer from dementia worldwide, a number that is expected to double in the next 20 years. Every study like this gives us renewed hope that effective treatments will be found sooner rather than later.
Part of the challenge in finding treatments for Alzheimer’s disease, the most common cause of dementia, is that we don’t yet know exactly what triggers it; a combination of factors is likely to be involved. Recent research has focused on how brain cells age and the many ways in which inherited genetics may play a role.
“We want to understand the early cellular changes that are found not only in Alzheimer’s disease, but also in other neurodegenerative diseases, including Parkinson’s disease and amyotrophic lateral sclerosis,” Selleck says.
“These results suggest a promising target for future treatments that could rescue the earliest abnormalities that occur.”
The research was published in iScience.
News Source : www.sciencealert.com
Gn Health
