Reelin, a protein essential for the plasticity of the cerebral cortex, is able to restore cognitive abilities in laboratory mice affected by Alzheimer's disease, according to one of the main findings of a paper published in the journal  Nature Communications which was led by researchers at the University of Barcelona, and in which  Rafael Maldonado, director of the Laboratory of Neuropharmacology, Department of Experimental and Health Sciences- UPF, has collaborated.

The work contributes to broaden the stage of research on new therapeutic targets against Alzheimer's, incorporating reelin and its signaling pathway as targets of study for the design of  new drugs. In fact, the researchers are planning to have, in just a few months, a system to identify chemical compounds that boost reelin signaling.

Restoring cognitive functions in laboratory models

Alzheimer's disease is a neurodegenerative disease characterized by the loss of connections between neurons and neuronal death. According to the new  preclinical study, the increase of levels of reelin protein in the brain prevents cognitive impairment in mice affected by  Alzheimer's. In addition, reelin also slows the process of fiber formation of the Aβ peptide in vitro, and reduces the accumulation of amyloid deposits in the brain of animals with the disease.

The double pathway of Aβ peptide and tau protein

Most studies on Alzheimer's seek pharmacological targets related to a specific process involved in the disease. However as an element of innovation this work examines the reelin - a synaptic and cognitive enhancer - signaling pathway which also regulates the amyloid precursor protein (APP) and tau protein, which are two proteins involved in basic processes of Alzheimer's disease.

The most toxic peptides in Alzheimer's disease

Experts also describe the way in which reelin is able to interact in vitro and reduce the toxicity of the Aβ42 peptide, which has a high tendency to fiber formation and aggregation in senile plaques. "The interaction of reelin with Aβ42 peptides, considered the most toxic in Alzheimer's disease according to current hypotheses, had not been described until now in any scientific study. This work shows for the first time that the toxicity of Aβ42 peptides on neurons is decreased in the presence of reelin" said to the authors.

In vitro work has demonstrated that reelin interacts with Aβ42 and delays the formation of fibers. These in vitro results have been reproduced in a mouse model of Alzheimer's disease in which it has been observed that reelin also reduces the formation of amyloid plaques. The work shows for the first time a neuroprotective effect of reelin in neurodegenerative diseases, demonstrated in vivo in laboratory models, and furthermore, it provides an explanatory hypothesis about this protective action.

(Extracted from a press release ​​by the UB)

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