One ‘click’ and everything changes. There is a switch that turns on the mechanism that contributes to the progression of Alzheimer’s disease. This was discovered by an international team of scientists, also composed of Italian researchers. Experts have turned the spotlight on a human antimicrobial peptide – LL-37 – which starts a process that plays a significant role: it activates the CLIC1 protein causing microglial hyperactivation, neuroinflammation and excitotoxicity. The peptide, explain the authors of a study published in ‘Molecular Psychiatry’, causes significant pathological phenotypes linked to Alzheimer’s including increased beta-amyloid, the formation of neurofibrillary tangles, neuronal death, brain atrophy, enlargement of the cerebral ventricles. and impaired synaptic plasticity. All this leads to a progressive cognitive deficit.
The discovery of candida LL-37 to become a possible therapeutic target, explain the researchers of the State University of Milan who, in collaboration with the Institute of Zoology of Kunming (China), contributed to the identification of the human antimicrobial peptide.
The tricolor research group, coordinated by Michele Mazzanti, had already conducted previous studies showing that the Clic1 protein, by modifying its localization from the cytoplasm to the cell membrane in the cells of the brain’s immune system, contributes to the onset and progression of Alzheimer’s disease. . But until now, the mechanisms of Clic1 formation and activation in this function remained unknown.
In the new study, the researchers found that LL-37 promotes the process. Blocking the interaction between LL-37 and Clic1 inhibits all of these phenotypes. “The Clic1 protein, once inserted into the cell membrane, has a fundamental function in the activation of immune cells that occurs during chronic inflammation phenomena and in particular those affecting the central nervous system as in the case of Alzheimer’s disease – explains Mazzanti. – The LL-37 peptide favoring the migration of the Clic1 protein in the membrane can be considered a promoter of the neurodegenerative process. Preventing the peptide from performing its function or directly inhibiting the protein localized in the membrane could be a pharmacological strategy to slow down or even block progression of the neurodegenerative process “, concludes the full professor of Physiology at the Department of Biosciences of the University.