Scientists from the CNRS and Grenoble Alpes University have discovered that the injection of a modified protein of the type “ pseudo-prion »[1] helps protect against Alzheimer’s disease. Their study carried out in mice was published in the journal Molecular Psychiatry [2].
One injection for an effect for several months
Alzheimer’s disease is a neurodegenerative disease that is caused by damage caused by the abnormal accumulation of two proteins, amyloid-β and Tau, in the brain. By modifying neurons and their synapses, they lead, “ eventually “, has ” the inability to create new memories “.
The injection of a mutated amyloid-β protein, with the so-called “mutation Icelandic »[3]in the hippocampus [4] of mice genetically modified to “ mimic Alzheimer’s disease “, made it possible to reduce inflammation, the accumulation of Tau proteins, damage to connections between neurons and cognitive disorders, indicates Marc Dhenain, researcher at the CNRS and the CEA.
A single administration was found to be sufficient to achieve protection, observed for 9 months so far.
Towards a new therapy?
The researchers hope that this result can be “ the starting point for a new category of preventive therapies » administered at an early stage.
Jacques Tremblay, a researcher at Laval University in Quebec, had already started work to develop a gene therapy which, using the gene editing tool Crispr-Cas9, would introduce the beneficial mutation “ in situ », in the genome of neurons.
However, injection into the human hippocampus is not ” not possible », Estimates doctor and researcher Philippe Amouyel, president of the France Alzheimer Foundation. According to him, “ we should try to mimic this effect with small molecules ”, which could be “ introduced into the brain by nanovectors “. For his part, even if he considers these latest results to be very interesting, Frédéric Checler from the Institute of Molecular and Cellular Pharmacology in Sophia Antipolis, recalls that cognitive effects have already been obtained in animals, without being subsequently observed in humans. ‘man.
[1] “ Abnormal prion proteins are generally responsible for serious neurodegenerative diseases such as mad cow disease or Creutzfeldt-Jakob disease. Their normal form is naturally present in our brain. When a prion protein changes shape, it becomes abnormal and other surrounding proteins adopt the same abnormal shape, which therefore amplifies the processes underway. The amyloid-β protein can also have this behavior, and is therefore considered a “pseudo-prion” “.
[2] Célestine, M., Jacquier-Sarlin, M., Borel, E. et al. Transmissible long-term neuroprotective and pro-cognitive effects of 1–42 beta-amyloid with A2T icelandic mutation in an Alzheimer’s disease mouse model. Mol Psychiatry (2024). https://doi.org/10.1038/s41380-024-02611-8
[3] By analyzing the entire genome of 1,795 Icelanders, Thorlakur Jonsson’s team identified a mutation present in certain inhabitants which has a protective effect against Alzheimer’s disease, but also ” normal neurocognitive decline “. This mutation, called “ A673T ”, is present in less than 1% of Scandinavian people. It is located on a gene coding for an amyloid precursor protein (APP).
[4] brain structure very involved in memory »
Sources: CNRS (06/14/2024); Le Monde, Hervé Morin (06/14/2024)
