Neuronal Cytoskeleton in Intellectual Disability: From Systems Biology and Modeling to Therapeutic Opportunities
Articolo
Data di Pubblicazione:
2021
Abstract:
Intellectual disability (ID) is a pathological condition characterized by limited intellectual
functioning and adaptive behaviors. It affects 1–3% of the worldwide population, and no pharmacological
therapies are currently available. More than 1000 genes have been found mutated in ID
patients pointing out that, despite the common phenotype, the genetic bases are highly heterogeneous
and apparently unrelated. Bibliomic analysis reveals that ID genes converge onto a few biological
modules, including cytoskeleton dynamics, whose regulation depends on Rho GTPases transduction.
Genetic variants exert their effects at different levels in a hierarchical arrangement, starting from
the molecular level and moving toward higher levels of organization, i.e., cell compartment and
functions, circuits, cognition, and behavior. Thus, cytoskeleton alterations that have an impact on cell
processes such as neuronal migration, neuritogenesis, and synaptic plasticity rebound on the overall
establishment of an effective network and consequently on the cognitive phenotype. Systems biology
(SB) approaches are more focused on the overall interconnected network rather than on individual
genes, thus encouraging the design of therapies that aim to correct common dysregulated biological
processes. This review summarizes current knowledge about cytoskeleton control in neurons and its
relevance for the ID pathogenesis, exploiting in silico modeling and translating the implications of
those findings into biomedical research.
Tipologia CRIS:
03B-Review in Rivista / Rassegna della Lett. in Riv. / Nota Critica
Keywords:
Disabilità Intellettiva
GTPasi
Citoscheletro
Elenco autori:
Carla Liaci, Mattia Camera , Giovanni Caslini, Simona Rando, Salvatore Contino, Valentino Romano, Giorgio Merlo
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