Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
13,978
result(s) for
"Mental Retardation"
Sort by:
The faces of intellectual disability : philosophical reflections
In a challenge to current thinking about cognitive impairment, this book
explores what it means to treat people with intellectual disabilities in an ethical
manner. Reassessing philosophical views of intellectual disability, Licia Carlson
shows how we can affirm the dignity and worth of intellectually disabled people
first by ending comparisons to nonhuman animals and then by confronting our fears
and discomforts. Carlson presents the complex history of ideas about cognitive
disability, the treatment of intellectually disabled people, and social and cultural
reactions to them. Sensitive and clearly argued, this book offers new insights on
recent trends in disability studies and philosophy.
eBook
MECP2 disorders: from the clinic to mice and back
Two severe, progressive neurological disorders characterized by intellectual disability, autism, and developmental regression, Rett syndrome and MECP2 duplication syndrome, result from loss and gain of function, respectively, of the same critical gene, methyl-CpG-binding protein 2 (MECP2). Neurons acutely require the appropriate dose of MECP2 to function properly but do not die in its absence or overexpression. Instead, neuronal dysfunction can be reversed in a Rett syndrome mouse model if MeCP2 function is restored. Thus, MECP2 disorders provide a unique window into the delicate balance of neuronal health, the power of mouse models, and the importance of chromatin regulation in mature neurons. In this Review, we will discuss the clinical profiles of MECP2 disorders, the knowledge acquired from mouse models of the syndromes, and how that knowledge is informing current and future clinical studies.
Journal Article
The molecular biology of FMRP: new insights into fragile X syndrome
Fragile X mental retardation protein (FMRP) is the product of the fragile X mental retardation 1 gene (FMR1), a gene that — when epigenetically inactivated by a triplet nucleotide repeat expansion — causes the neurodevelopmental disorder fragile X syndrome (FXS). FMRP is a widely expressed RNA-binding protein with activity that is essential for proper synaptic plasticity and architecture, aspects of neural function that are known to go awry in FXS. Although the neurophysiology of FXS has been described in remarkable detail, research focusing on the molecular biology of FMRP has only scratched the surface. For more than two decades, FMRP has been well established as a translational repressor; however, recent whole transcriptome and translatome analyses in mouse and human models of FXS have shown that FMRP is involved in the regulation of nearly all aspects of gene expression. The emerging mechanistic details of the mechanisms by which FMRP regulates gene expression may offer ways to design new therapies for FXS.Inactivation of the gene encoding fragile X mental retardation protein (FMRP) drives the impairments in brain development and function that underlie fragile X syndrome. Richter and Zhao illustrate how innovative genetic and molecular biology tools have enhanced our understanding of both FMRP’s function and the causes of fragile X syndrome pathophysiology.
Journal Article
Targeting G-quadruplex DNA as cognitive function therapy for ATR-X syndrome
Alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome is caused by mutations in
ATRX
, which encodes a chromatin-remodeling protein. Genome-wide analyses in mouse and human cells indicate that ATRX tends to bind to G-rich sequences with a high potential to form G-quadruplexes. Here, we report that
Atrx
mutation induces aberrant upregulation of Xlr3b expression in the mouse brain, an outcome associated with neuronal pathogenesis displayed by ATR-X model mice. We show that ATRX normally binds to G-quadruplexes in CpG islands of the imprinted
Xlr3b
gene, regulating its expression by recruiting DNA methyltransferases. Xlr3b binds to dendritic mRNAs, and its overexpression inhibits dendritic transport of the mRNA encoding CaMKII-α, promoting synaptic dysfunction. Notably, treatment with 5-ALA, which is converted into G-quadruplex-binding metabolites, reduces RNA polymerase II recruitment and represses
Xlr3b
transcription in ATR-X model mice. 5-ALA treatment also rescues decreased synaptic plasticity and cognitive deficits seen in ATR-X model mice. Our findings suggest a potential therapeutic strategy to target G-quadruplexes and decrease cognitive impairment associated with ATR-X syndrome.
In a mouse model of intellectual disability, the chromatin remodeling protein ATR-X is shown to bind to G-quadruplex DNA structures and modulate target gene expression, which can be pharmacologically targeted to restore neuronal and cognitive phenotypes in these animals.
Journal Article
Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics
Fragile X syndrome (FXS) is the most frequent form of inherited intellectual disability and is also linked to other neurologic and psychiatric disorders. FXS is caused by a triplet expansion that inhibits expression of the FMR1 gene; the gene product, FMRP, regulates mRNA metabolism in the brain and thus controls the expression of key molecules involved in receptor signaling and spine morphology. While there is no definitive cure for FXS, the understanding of FMRP function has paved the way for rational treatment designs that could potentially reverse many of the neurobiological changes observed in FXS. Additionally, behavioral, pharmacological, and cognitive interventions can raise the quality of life for both patients and their families.
Journal Article