Abstract
Autism is an umbrella diagnosis with several different etiologies. Fragile X syndrome (FXS), one of the first identified and leading causes of autism, has been modeled in mice using molecular genetic manipulation. These Fmr1 knockout mice have recently been used to identify a new putative therapeutic target, the metabotropic glutamate receptor 5 (mGluR5), for the treatment of FXS. Moreover, mGluR5 signaling cascades interact with a number of synaptic proteins, many of which have been implicated in autism, raising the possibility that therapeutic targets identified for FXS may have efficacy in treating multiple other causes of autism.
Highlights
Leo Kanner first described autism in 1943 [1]
Standardization of diagnostic criteria [2], and improvements in our ability to reliably detect chromosomal abnormalities [14] allowed for the identification in the early 1980’s of the first genetic cause of autism—Fragile X syndrome (FXS) [15,16,17]
This response to stimulation with DHPG parallels spine changes seen in the Fmr1 knockout mouse (Fmr1 KO) mice, which lent support to the theory that exaggerated signaling through metabotropic glutamate receptor 5 (mGluR5) in the absence of FMRP could account for this morphologic correlate of synaptic plasticity [61]
Summary
Leo Kanner first described autism in 1943 [1]. It wasn’t until 1980 that autism was formally recognized in the Diagnostic and Statistical Manual of Mental disorders (DSM-III), and included as part of a new class, the Pervasive Developmental Disorders (PDD) [2]. FMRP is an RNA binding protein that colocalizes with polyribosomes [44, 47,48,49,50,51,52,53,54,55] which are found at the base of dendritic spines where they are thought to mediate local translational control of the synapse [56] Both in vitro and in vivo metabolic labeling studies have directly shown that FMRP functions as a repressor of protein synthesis [57,58,59,60].
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