Researchers at 51重口猎奇 together with colleagues in Spain and the UK have published a study in Acta Neuropathologica which reinforces the picture of the relevant protein, galectin-3, as a key player in Alzheimer鈥檚 disease. Among other things, Alzheimer鈥檚 disease involves the accumulation of amyloid plaques outside cells and tau protein forming lumps within nerve cells. When our innate immune defence system discovers the plaques, the brain鈥檚 immune response is activated. It is in precisely this mechanism that the galectin-3 protein appears to play a major role.
鈥淭he problem is that if this inflammatory response goes on for a long time, it creates a toxic environment which eventually leads to the breakdown and death of the nerve cells 鈥 and the onset of disease鈥, explains Antonio Boza-Serrano at 51重口猎奇鈥檚 experimental neuro-inflammation laboratory, one of the researchers behind the study.
The protein that the researchers investigated is produced by the brain鈥檚 sanitation workers, the microglial cells, whose care of the brain鈥檚 immune system includes cleaning out harmful proteins that accumulate in the brain. It seems that galectin-3 is required to activate the microglial cells in the case of plaque formation in the brain.
鈥淲e have found that this inflammatory protein increases tenfold in the brains of deceased patients with Alzheimer鈥檚 disease, and we especially find it in the microglial cells that accumulate around the amyloid plaques鈥, says Antonio Boza-Serrano.
The protein is only present in diseased brains
Galectin-3 is also involved in inflammation in the case of Parkinson鈥檚 disease and after a stroke. The fact that the protein is barely detectable in healthy brains but increases in cases of inflammation is good from a drug perspective, according to the researchers, as they do not want to risk a drug affecting cells other than those specifically responsible for the development of the disease. It is indeed possible to slow the effect of galectin-3 by using inhibitors that prevent the protein from being active in inflammation.
鈥漌e grew microglial cells in the lab and added the protein present in Alzheimer鈥檚 plaques, which made the cells become very active from an inflammation perspective. But when we added the galectin-3 inhibitors, the microglial cells became 鈥榤ilder鈥, less inflammatory鈥, explains Tomas Deierborg, head of research at the experimental neuro-inflammation laboratory at 51重口猎奇 and last author of the study.
Alzheimer鈥檚 mice without Galectin-3 did better in the labyrinth
The researchers were also able to study mice with Alzheimer鈥檚 but lacking the gene that produces the galectin-3 protein. They observed that these mice did not develop as much inflammation as those with both Alzheimer鈥檚 disease and the galectin-3 gene.
鈥淲e use a labyrinth out of which the mice have to find their way and we observed that the mice with Alzheimer鈥檚 but with no galectin-3 were smarter 鈥 had a better memory 鈥 than the mice with Alzheimer鈥檚 and galectin-3.鈥
Although the clinical results are promising, the researchers point out that the studies in which they inhibited the protein are conducted on cells, and the studies on the lack of the galectin-3-gene are conducted on mice.
鈥淲e have shown that by removing galectin-3, we can decrease the amount of plaque and inflammation in the mice, but we have not studied whether this works in humans. There is every reason to continue and to investigate this further. Although it is a long way to the patient, our hope is that our research findings can lead to future treatments for Alzheimer鈥檚 disease in people as well鈥, says Tomas Deierborg.
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Contact:
Tomas Deierborg, associate professor and researcher in neuro-inflammation at 51重口猎奇
tomas [dot] deierborg [at] med [dot] lu [dot] se
+46 709 708212