Scientists discover a way to prevent cell death, but how will this affect treatment for patients with Alzheimer’s disease?
A recent study published in Nature aimed to unravel the relationship between Alzheimer’s Disease (AD) and neuronal loss. The study highlighted the primary driver behind neuronal death in Alzheimer's: necroptosis, a form of programmed cell death. This process occurs during the development of AD when neurons are exposed to amyloid plaques and tau tangles - two hallmark features implicated in AD.
This newfound research not only provides insight into the intricacies of Alzheimer's but also hints that there may be potential to target specific pathways and genes in new therapeutic approaches.
A new model: From mice to humans
While prior studies hinted at the mechanisms of cell death in AD, this study underscores the limitations of past models as the pathology was trigged though external interventions and therefore, unable to demonstrate the natural pathology in humans. Building on an established xenotransplantation model, the researchers proposed a new model: transplanting human neurons into a mouse brain engineered to develop amyloid plaques, allowing for greater exploration of AD pathology over time.
Remarkably, the model revealed that amyloid plaques alone were insufficient to induce Alzheimer's-like pathology in mouse neurons. This emphasised a human-specific vulnerability, as transplanted human neurons exhibited AD features in the presence of amyloid pathology, where the control mice did not. This suggests a distinctive susceptibility of human neurons to changes associated with AD.
Decoding gene expression: What is MEG3?
Through gene expression analysis, the researchers identified that the long non-coding RNA, MEG3, was strongly expressed in human neurons in response to amyloid plaques. The upregulation of MEG3 was a key finding, suggesting its potential involvement in the pathological processes associated with AD.
Potential avenues for treatment
Ultimately, the study highlights the road for several exciting potential treatments:
Reducing the levels of MEG3 led to the prevention of cell death, suggesting the potential to target MEG3 expression.
Necroptosis is an active area of drug development in other conditions like cancer and ALS, so may hold potential for repurposing or developing new inhibitors specific to AD.
Where do we go from here?
While the discovery of MEG3 and its role in necroptosis provides a promising direction for AD research, the journey from discovery to effective human treatments is complex and involves rigorous testing and validation. Realistic hope exists, but successful translation will require continued research, collaboration, and careful clinical development. Additionally, advancements in our understanding of AD and the development of targeted therapies will likely be incremental, involving a combination of approaches to address the multifaceted nature of the disease.
Photo by Robina Weermeijer on Unsplash
This article was written by Rebecca Parker and edited by Julia Dabrowska. Interested in writing for WiN UK yourself? Contact us through the blog page and the editors will be in touch!
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