Meeting at the crossroads: common mechanisms in Fragile X and Down syndrome.
Intellectual disability is characterized by significantly impaired cognitive abilities and is due to various etiological factors, including both genetic and non-genetic causes. Two of the most common genetic forms of intellectual disability are Fragile X syndrome (FXS) and Down syndrome (DS). Recent studies have shown that proteins altered in FXS and DS can physically interact and participate in common signaling pathways regulating dendritic spine development and local protein synthesis, thus supporting the notion that spine dysmorphogenesis and abnormal local protein synthesis may be molecular underpinnings of intellectual disability. Here we review the molecular constituents regulating local protein synthesis and spine morphology and their alterations in FXS and DS. We argue that these changes might ultimately affect synaptic homeostasis and alter cognitive performance.
Zilkha Neurogenetic Institute and Department of Cell and Neurobiology, University of Southern California, Los Angeles, CA 90033, USA.
Karen T
KT
Chang
Hyunah
H
Ro
Wei
W
Wang
Kyung-Tai
KT
Min
D000818:Animals; D004268:DNA-Binding Proteins; D049229:Dendritic Spines / Q000473:pathology; D004314:Down Syndrome / Q000235:genetics* / Q000473:pathology; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics* / Q000378:metabolism; D005600:Fragile X Syndrome / Q000235:genetics* / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; C497683:FMR1 protein, human; C108612:RCAN1 protein, human