Researchers have identified a class of proteins that play a crucial role in cell repair and growth-signaling systems, offering a potential new avenue for treating Alzheimer’s disease and other neurodegenerative conditions. By disrupting specific sugar modifications of these proteins, cell repair can be promoted, leading to the reversal of cellular abnormalities associated with neurodegenerative diseases.
The findings of this study, published in the journal iScience, shed light on a novel approach that could have significant implications in the field of neurodegenerative disease research. The researchers, led by a team at Penn State, have also secured a patent related to this discovery.
Traditional strategies for treating Alzheimer’s disease have typically focused on addressing changes that manifest in the later stages of the condition. While some recently approved drugs have shown limited effectiveness in slowing the disease progression by targeting amyloid accumulation, the researchers emphasize the importance of addressing early cellular deficits to halt or reverse the disease process. By identifying common cellular changes present in Alzheimer’s, Parkinson’s, and ALS, the team aims to uncover new treatment opportunities.
Alzheimer’s disease affects approximately 6.9 million Americans aged 65 and older, yet its biological cause remains unclear. Heparan sulfate-modified proteins have been implicated in the development of Alzheimer’s, but their specific role has been elusive. Through a series of experiments involving human cell lines and mouse brain cells, the researchers demonstrated that these proteins regulate critical cellular processes affected in various neurodegenerative diseases.
Heparan sulfate-modified proteins, found on cell surfaces and within the cell matrix, play a vital role in cell signaling and growth regulation. These proteins, named after a sugar polymer called heparan sulfate, form signaling complexes that influence cell growth, environmental interactions, and the process of autophagy – a cellular repair mechanism that clears damaged components.
In neurodegenerative diseases, early-stage impairments in autophagy lead to reduced cellular repair capacity. By disrupting the sugar modifications of heparan sulfate-modified proteins, the researchers observed increased autophagy levels, enhancing the cell’s ability to repair damage.
In both human and mouse cells, reducing the function of heparan sulfate-modified proteins not only boosted autophagy levels but also improved mitochondrial function and reduced lipid accumulation within cells – addressing key early-stage pathologies in neurodegenerative conditions.
Further investigations in an Alzheimer’s disease animal model revealed that manipulating heparan sulfate-modified proteins could mitigate neuronal death and correct other cellular defects. These findings align with recent genetic research in humans, indicating the potential relevance of this pathway in Alzheimer’s pathology.
By targeting the enzymes responsible for heparan sulfate production, the researchers suggest a promising approach to preventing neurodegeneration in humans by addressing early cellular abnormalities in Alzheimer’s.
The study also explored the impact of disrupting heparan sulfate chains on gene expression in human cells, revealing significant alterations in genes associated with late-onset Alzheimer’s, including APOE.
Looking ahead, the researchers believe that targeting heparan sulfate-modified proteins to enhance cell repair systems could have broad implications for treating various diseases characterized by autophagy defects.
The potential applications of this research extend beyond Alzheimer’s disease and could be relevant to a wide range of medical conditions with similar cellular abnormalities. The team at Penn State, along with collaborators from other institutions, received support from the National Institutes of Health and the Penn State Eberly College of Science for this groundbreaking work.
