Cell signaling pathways in autosomal-dominant leukodystrophy  (ADLD): the intriguing role of the astrocytes.

Cell signaling pathways in autosomal-dominant leukodystrophy (ADLD): the intriguing role of the astrocytes. Cell Mol Life Sci. 2020 Oct 09;: Authors: Ratti S, Rusciano I, Mongiorgi S, Owusu Obeng E, Cappellini A, Teti G, Falconi M, Talozzi L, Capellari S, Bartoletti-Stella A, Guaraldi P, Cortelli P, Suh PG, Cocco L, Manzoli L, Ramazzotti G Abstract Autosomal-dominant leukodystrophy (ADLD) is a rare fatal neurodegenerative disorder with overexpression of the nuclear lamina component, Lamin B1 due to LMNB1 gene duplication or deletions upstream of the gene. The molecular mechanisms responsible for driving the onset and development of this pathology are not clear yet. Vacuolar demyelination seems to be one of the most significant histopathological observations of ADLD. Considering the role of oligodendrocytes, astrocytes, and leukemia inhibitory factor (LIF)-activated signaling pathways in the myelination processes, this work aims to analyze the specific alterations in different cell populations from patients with LMNB1 duplications and engineered cellular models overexpressing Lamin B1 protein. Our results point out, for the first time, that astrocytes may be pivotal in the evolution of the disease. Indeed, cells from ADLD patients and astrocytes overexpressing LMNB1 show severe ultrastructural nuclear alterations, not present in oligodendrocytes overexpressing LMNB1. Moreover, the accumulation of Lamin B1 in astrocytes induces a redu...
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research