The PIN1 protein plays a fundamental role in the structure of the cell nucleus and in protecting the DNA contained in them from mechanical stress. When absent or present in low levels, as it occurs in the neurons of Alzheimer’s disease, DNA loses its organization, inflammation is produced and cells degenerate. This is the mechanism investigated in the study recently published in Cell Reports coordinated by Prof. Giannino Del Sal and carried out by ICGEB, UNITS, IFOM of Milan, with the collaboration of SISSA.
The key role of PIN1 in regulating certain physiological processes was already known: high levels of this protein in cells are associated with the appearance of tumours and metastases while low levels or its total absence are found in the case of degenerative diseases such as Alzheimer’s. This study focuses on understanding the molecular mechanisms that lead to cell degeneration in the absence or in cases of low levels of PIN1. It shows the role of the protein in limiting the anomalous activation of mobile elements of the cell genome, so-called transposons, which are mainly responsible for DNA damage.
“It was shown that the function of Dodo/Pin1 is conserved from fruitfly to vertebrates, including humans, and it is crucial to prevent neurodegeneration triggered by anomalous mobilization of transposable elements.” Says Antonello Mallamaci, who leads the Cerebral Cortex Development Lab at SISSA that contributed to modelling of these phenomena in murine cortico-cerebral cells.
The study involves also SISSA Computational Genomics Lab, as its Head Remo Sanges says: “Our lab contributed to the bioinformatics and experimental analysis by developing and applying novel specific strategies for the identification and quantification of transposable elements activity”.
The research paves the way to the pharmacological modulation of the levels of the protein to prevent or improve the course of diseases such as Alzheimer’s.