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Brain cell death could be a natural, healthy process

Scientists have found that inhibiting neuronal death could actually do more harm than good
by TR Pakistan

Scientists at the Champalimaud Centre for the Unknown (CCU), in Lisbon, Portugal have demonstrated that the death of neuronal cells associated with Alzheimer’s Disease (AD) is not the disaster it was previously thought to be. Rather, it is the result of a biological quality control mechanism trying to prevent the accumulation of malfunctioning neurons.

This quality control mechanism is referred to as cell competition. The fittests cells in a tissue are selected, through a natural “fitness comparison” between neighboring cells. This triggers the suicide of less fit cells by their healthier neighbors.

Cell competition is a normal, powerful anti-aging mechanism in the body in general but in the brain in particular.

Read more: Hidden region of the human brain discovered

“In 2015, we discovered that clearing unfit cells from a tissue was a very important anti-aging mechanism to preserve organ function,” says Eduardo Moreno, principal investigator of the Cell Fitness lab at the CCU.

Moreno’s team argues that if these fitness comparisons happened in normal aging, they could also be involved in neurodegenerative diseases associated with accelerated aging, such as Alzheimer’s, Parkinson’s disease or Huntington’s disease.

The team bred fruit flies that had been genetically manipulated to express the human amyloid-beta protein in their brain, which forms aggregates in the brains of AD patients. The formation of amyloid-β aggregates in the brain is a crucial step in the development of AD.

These flies displayed symptoms and pathologies similar to those of AD patients: “they showed loss of long-term memory, accelerated aging of the brain and motor coordination problems, all of which got worse with age”, specifies Christa Rhiner, whose team studied the cognitive and motor functions of the flies. Moreno points out that the neuronal deaths occurring in these flies was not occurring on their own but being triggered through cell competition. Furthermore, when neuronal death was blocked, the flies developed memory problems, experienced a greater loss in motor coordination and died earlier. Furthermore, when the neuronal death process were boosted, the flies expressing the AD-associated amyloid-beta proteins showed an impressive recovery. “The flies almost behaved like normal flies with regard to memory formation, locomotive behavior and learning”, says Rhiner.

“Our most important finding is that we have probably been thinking the wrong way about Alzheimer’s disease. Our results suggest that neuronal death is beneficial because it removes neurons that are affected by noxious beta-amyloid aggregates from brain circuits, and having those dysfunctional neurons is worse than losing them” Moreno concludes.

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