A new study from the University of Liverpool marks a significant step forward in scientists’ understanding of Alzheimer’s disease.
Researchers have shed new light on how mechanical signals in the brain are disrupted and can lead to the condition responsible for 60-80% of dementia cases worldwide.
The team of researchers, led by Professor Ben Goult from the University of Liverpool, have investigated the role of two proteins in the brain and suggest that the stability of their relationship with each other is crucial for the formation and maintenance of memory. Disruptions in this mechanical signaling pathway can lead to the disease. This is the first time this association has been identified and could pave the way for therapeutic interventions.
The recently published paper proposes that Amyloid Precursor Protein (APP), known for its role in the formation of the amyloid plaques in the brain that are a characteristic feature of Alzheimer’s disease (AD), interacts directly with talin, a synaptic scaffold protein. For the first time, it is suggested that the talin-APP interaction is crucial for the mechanical integrity of synapses in the brain and that the misprocessing of APP observed in Alzheimer’s disease disrupts mechanical signaling pathways, leading to synaptic degeneration and memory loss. thus contributing to the progression of AD. The paper goes on to show that when talin is removed from cells in culture, APP processing changes dramatically.
Professor Ben Goult, University of Liverpool said: “Alzheimer’s disease is a brutal neurodegenerative disorder characterized by memory loss and cognitive decline. It is a global health challenge, yet little is known about the underlying mechanisms that lead to the disease. However, this article gives us a new piece of the puzzle and advances research considerably.
“Our paper outlines that APP is fundamental to the mechanical coupling of synapses in the brain and how APP processing is part of a mechanical signaling pathway that maintains synaptic integrity. Improper processing of APP, due to altered mechanical signals, however, disrupts this path.” What’s most exciting is that our paper highlights the intriguing possibility that repurposing currently available cancer drugs that stabilize focal adhesions could be a path to recovery. mechanical integrity at synapses Although this is currently only a theoretical prediction, our current research is aimed at testing whether this is a novel approach to slowing the progression of Alzheimer’s disease.
“Further research is needed to test the theories emerging from these new findings. However, this marks an important moment in better understanding this disease and could bring us closer to an early diagnosis and treatment.”
Source:
Magazine reference:
Ellis, C., et al. (2024). The structure of an amyloid precursor protein/talin complex suggests a mechanistic basis of Alzheimer’s disease. Open Biology. doi.org/10.1098/rsob.240185.