A small protein hidden in our body, a powerful antimicrobial agent that protects us from infections: it is called the LL-37 peptide and is responsible for activating the mechanism that triggers the progression, hence the worsening, of Alzheimer’s disease. The discovery is Italian-Chinese: it comes from researchers at the State University of Milan, in collaboration with the Institute of Zoology of Kunming (China). The study was published in Molecular Psychiatrythe group’s magazine Nature. And it is precisely this new knowledge that opens the doors to long-awaited results in terms of targeted therapies against Alzheimer’s.
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The missing piece
The research group of the State University of Milan, coordinated by Michele Mazzanti, Professor of Physiology in the Department of Biosciences, had already conducted studies on the subject, focusing however on the role of the CLIC1 protein. In practice, the experts had shown that the CLIC1 protein, by modifying its localization from the cytoplasm (all the portion of a cell contained within the cell membrane) to the cell membrane of the cells of the brain’s immune system, contributes to the birth and worsening of Alzheimer’s. But one piece was missing from the procedure: because the mechanisms of formation and activation of the CLIC1 protein in this function remained unknown. Piece that the Italian-Chinese researchers have brought to light with this latest work.
The mechanisms that trigger the disease
In the newly published study, the researchers found that another protein, the human antimicrobial peptide LL-37, promotes the movement and integration of the CLIC1 protein into the cell membrane. Which in practice activates the other protein causing microglial hyperactivation (group of “sentinel immune cells”), but also neuroinflammation (which is the response of the central nervous system to external and internal attacks, such as infections, injuries, diseases, abnormal neuronal activity ) and excitotoxicity (phenomenon of neuronal toxicity resulting from exposure to relatively high concentrations of glutamic acid).
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The photograph of the protein attacking the brain
But what are antimicrobial peptides (Amp)? Also called host defense peptides (Hdp) are part of the innate immune response found in all life classes. These are small protein molecules made up of 12-50 amino acids and widely spread in nature. Peptides with biological activity have in fact been isolated from a large number of organisms, belonging to both the plant and animal kingdom, such as bacteria, plants, insects, amphibians and mammals. At present, about 800 substances classified in this way are known.
The role in innate immunity
Their role is important because they play a fundamental action in the so-called innate or natural immunity, which consists of a series of defense mechanisms directed towards a wide spectrum of microorganisms and present in the individual from birth. Pre-existing mechanisms to the exposure of a possible foreign substance (antigen), which represent the first real defense barrier of the organism to pathogens.
In particular, some peptides have been shown to effectively fight both Gram-positive and Gram-negative bacteria, yeasts of the genus Candida, but are also able to inhibit the replication of some viruses.
The consequences on cognitive activity
The discovery of the international research team highlighted the effects of the action of the LL-37 peptide protein. He found that it causes significant pathological phenotypes (the phenotype is the set of all the characteristics manifested by a living organism) linked to Alzheimer’s, including the increase in β-amyloid, the formation of neurofibrillary tangles (plaques), death neuronal, cerebral atrophy, the enlargement of the cerebral ventricles and the impairment of synaptic plasticity, that is the ability of the nervous system to modify the intensity of interneuronal relationships, to establish new ones and to eliminate some of them.
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Working on new strategies
So, having made this discovery, how will it be possible to make it fruitful to prevent Alzheimer’s not only born but worsened? “The CLIC1 protein, once inserted into the cell membrane, has a fundamental function in the activation of immune cells, which occurs during chronic inflammation phenomena, and in particular those affecting the central nervous system, as in the case of Alzheimer’s disease. – underlines Mazzanti -. The LL-37 peptide, favoring the migration of the CLIC1 protein in the membrane, can be considered a promoter of the neurodegenerative process. a pharmacological strategy to slow down or even block the progression of the neurodegenerative process “.
Alzheimer’s in figures
There are over 1 million and 480 thousand people living with dementia in Italy today, and it is estimated that they are destined to become 2 million and 300 thousand by 2050: approximately 900 thousand more people will therefore need assistance and post-support diagnostic.
The data emerged from research on the prevalence of dementia globally conducted by the University of Washington’s Institute of Health Metrics and Evaluation and published in the journal Lancet.
According to experts, not only are they worrying, but they even underestimate the true extent of the problem. And globally, if possible, the situation is even more critical: around the world there are 55 million people with dementia, destined to become 139 million by 2050. Every 3 seconds, according to the researchers’ estimates, someone in the world develops the illness.