Mechanisms Underlying Circuit Dysfunction in Neurodevelopmental Disorders.
Annu Rev Genet
; 56: 391-422, 2022 11 30.
Article
en En
| MEDLINE
| ID: mdl-36055969
ABSTRACT
Recent advances in genomics have revealed a wide spectrum of genetic variants associated with neurodevelopmental disorders at an unprecedented scale. An increasing number of studies have consistently identified mutations-both inherited and de novo-impacting the function of specific brain circuits. This suggests that, during brain development, alterations in distinct neural circuits, cell types, or broad regulatory pathways ultimately shaping synapses might be a dysfunctional process underlying these disorders. Here, we review findings from human studies and animal model research to provide a comprehensive description of synaptic and circuit mechanisms implicated in neurodevelopmental disorders. We discuss how specific synaptic connections might be commonly disrupted in different disorders and the alterations in cognition and behaviors emerging from imbalances in neuronal circuits. Moreover, we review new approaches that have been shown to restore or mitigate dysfunctional processes during specific critical windows of brain development. Considering the heterogeneity of neurodevelopmental disorders, we also highlight the recent progress in developing improved clinical biomarkers and strategies that will help to identify novel therapeutic compounds and opportunities for early intervention.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Trastornos del Neurodesarrollo
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Annu Rev Genet
Año:
2022
Tipo del documento:
Article
País de afiliación:
Reino Unido