In an exciting development scientists may have just figured out the reason how brain cells die in Alzheimer’s disease.
In a breakthrough discovery, scientists from the UK and Belgium have unraveled the mechanism behind brain cell death in Alzheimer’s disease. This long-standing mystery has been a subject of scientific debate for decades, but this recent revelation, published in the prestigious journal Science, sheds light on the role of abnormal proteins, collectively known as “necroptosis,” a type of programmed cell death. This groundbreaking finding has been hailed as “cool” and “exciting” for its potential to pave the way for novel treatment approaches for this debilitating condition.
The researchers observed that the accumulation of abnormal amyloid proteins in the brain triggers inflammation, which disrupts the delicate balance within neurons. This disruption leads to the formation of tau tangles, which further destabilize the neurons. As a result, these vulnerable cells activate a self-destruction pathway called necroptosis, a mechanism normally employed by the body to eliminate unwanted cells.
This finding represents a major step forward in understanding the pathogenesis of Alzheimer’s disease. By targeting the necroptosis pathway, researchers may develop novel therapeutic strategies to halt the progression of the disease and protect neurons from premature death.
The research team’s findings stem from experiments involving human brain cells transplanted into the brains of genetically modified mice engineered to produce excessive amounts of abnormal amyloid. This experimental approach enabled the researchers to directly observe the impact of amyloid accumulation on brain cell survival.
Blocking the production of MEG3 allowed the brain cells to survive, demonstrating the crucial role of this molecule in the demise of neurons in Alzheimer’s disease.
The identification of necroptosis as a key player in the neurodegeneration associated with Alzheimer’s disease provides valuable insights for future treatment development. With this knowledge, researchers can focus on developing drugs or therapies that specifically target and modulate this pathway, potentially offering a lifeline to millions of individuals affected by this devastating disease.
Abstract
Neuronal cell loss is a defining feature of Alzheimer’s disease (AD), but the underlying mechanisms remain unclear. We xenografted human or mouse neurons into the brain of a mouse model of AD. Only human neurons displayed tangles, Gallyas silver staining, granulovacuolar neurodegeneration (GVD), phosphorylated tau blood biomarkers, and considerable neuronal cell loss. The long noncoding RNA MEG3 was strongly up-regulated in human neurons. This neuron-specific long noncoding RNA is also up-regulated in AD patients. MEG3 expression alone was sufficient to induce necroptosis in human neurons in vitro. Down-regulation of MEG3 and inhibition of necroptosis using pharmacological or genetic manipulation of receptor-interacting protein kinase 1 (RIPK1), RIPK3, or mixed lineage kinase domain-like protein (MLKL) rescued neuronal cell loss in xenografted human neurons. This model suggests potential therapeutic approaches for AD and reveals a human-specific vulnerability to AD.