Researchers identify a new cell mechanism that connects Alzheimer’s disease and cancers

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his image shows the developing brain visualized with fluorescence laser scanning microscopy. It illustrates the neurons (blue) and growing axons (red and green). The image is credited to INc-UAB.

Age is the most important factor in the development of neurodegenerative diseases such as Alzheimer’s and cancer.

Moreover, epidemiological studies indicate that there is an inverse correlation between suffering from Alzheimer’s disease and cancer, although the mechanisms connecting these two pathologies remain unknown.

An international team of researchers led by Dr Carles Saura from the Institute of Neuroscience at UAB has unravel a mechanism crucial for the growth of neuron axons, a key process for the correct development of the brain.

According to the study, published in eLife, this mechanism requires presenilin, the main gene mutated in familial Alzheimer’s disease.

Its malfunction in this disease is what causes the abnormal accumulation of beta-amyloid in the brain in Alzheimer’s disease patients.

In this study, researchers demonstrate that presenilin is not only essential for regulating growth of neurons during brain development, but that it achieves this through the EphA3 receptor, a protein involved in several cancers.

The relevance of this study is that it demonstrates the existence of a new cell mechanism that connects neurodegeneration with cancer.

“The discovery of this new signalling route is very relevant in the study of neurological disorders in which the morphology of the neuron axon is altered.

Indeed, the implications of the study go beyond the brain given that the mechanism involves the EphA receptors, which play a key role in cancer”, explains first author of the study Dr. Míriam Javier.

According to Dr. Saura, “this research allows us to be optimistic about the development of common therapeutic strategies to fight neurological disorders and cancer.”


Alzheimer’s disease (AD) and cancer are among the leading causes of human death around the world. While neurodegeneration is the main feature of AD, the most important characteristic of malignant tumors is cell proliferation, placing these two diseases in opposite sides of cell division spectrum.

Interestingly, AD and cancer’s pathologies consist of a remarkable common feature and that is the presence of active cell cycle in both conditions. In an in vitro model of primary adult neuronal culture, we previously showed that treating cell with beta amyloid forced neurons to start a cell cycle.

Instead of cell division, however, neuronal cell cycle was aborted and a massive neurodegeneration was left behind as the consequence. A high level of cell cycle entry, which is a requirement for cancer pathogenesis, was reported in clinically diagnosed cases of AD, leading to neurodegeneration.

The diverse clinical manifestation of a similar etiology, have puzzled researchers for many years. In fact, the evidence showed an inverse association between AD and cancer prevalence, suggesting that switching pathogenesis toward AD protects patients against cancer and vice versa.

In this mini review, we discussed the possibility of involvement of cell proliferation and survival dysregulation as the underlying mechanism of neurodegeneration in AD, and the leading event to develop both disorders’ pathology.

As examples, the role of phosphoinositide 3 kinase/Akt/ mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway in cell cycle re-entry and blocking autophagy are discussed as potential common intracellular components between AD and cancer pathogenesis, with diverse clinical diagnosis.


Source:
UAB
Media Contacts:
Roser Bastida Barau – UAB
Image Source:
The image is credited to INc-UAB.

Original Research: Open access
“Presenilin/γ-secretase-dependent EphA3 processing mediates axon elongation through non-muscle myosin IIA”. Míriam Javier-Torrent, Sergi Marco, Daniel Rocandio, Maria Pons-Vizcarra, Peter W Janes, Martin Lackmann, Joaquim Egea, Carlos A Saura.
eLife doi:10.7554/eLife.43646.

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