scholarly journals Role of microRNA Pathway in Mental Retardation

2007 ◽  
Vol 7 ◽  
pp. 146-154 ◽  
Author(s):  
Abrar Qurashi ◽  
Shuang Chang ◽  
Peng Jin
Keyword(s):  
Mental Retardation ◽  
Fragile X Syndrome ◽  
Genetic Basis ◽  
Fragile X ◽  
Biological Pathways ◽  
Fragile X Mental Retardation ◽  
Mental Retardation Protein ◽  
Mirna Pathway ◽  
Microrna Pathway

Deficits in cognitive functions lead to mental retardation (MR). Understanding the genetic basis of inherited MR has provided insights into the pathogenesis of MR. Fragile X syndrome is one of the most common forms of inherited MR, caused by the loss of functional Fragile X Mental Retardation Protein (FMRP).MicroRNAs (miRNAs) are endogenous, single-stranded RNAs between 18 and 25 nucleotides in length, which have been implicated in diversified biological pathways. Recent studies have linked the miRNA pathway to fragile X syndrome. Here we review the role of the miRNA pathway in fragile X syndrome and discuss its implication in MR in general.

Role of microRNA pathway in Fragile X mental retardation

MicroRNAs ◽  
2009 ◽  
pp. 363-371
Author(s):  
Keith Szulwach ◽  
Peng Jin ◽  
Sidney Altman ◽  
Victor R. Ambros
Keyword(s):  
Mental Retardation ◽  
Fragile X ◽  
Fragile X Mental Retardation ◽  
Microrna Pathway

scholarly journals Decreased Nociceptive Sensitization in Mice Lacking the Fragile X Mental Retardation Protein: Role of mGluR1/5 and mTOR

2007 ◽  
Vol 27 (51) ◽  
pp. 13958-13967 ◽  
Author(s):  
T. J. Price ◽  
M. H. Rashid ◽  
M. Millecamps ◽  
R. Sanoja ◽  
J. M. Entrena ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Fragile X ◽  
Nociceptive Sensitization ◽  
Fragile X Mental Retardation ◽  
Mental Retardation Protein

scholarly journals The Fragile X Mental Retardation Protein: A Valuable Partner in the Battle against Epileptogenesis

2009 ◽  
Vol 9 (4) ◽  
pp. 116-118 ◽  
Author(s):  
Lisa R. Merlin
Keyword(s):  
Mental Retardation ◽  
Fragile X Syndrome ◽  
Metabotropic Glutamate Receptor ◽  
Mossy Fiber ◽  
Fragile X ◽  
Critical Role ◽  
Fmr1 Gene ◽  
Metabotropic Glutamate ◽  
Fragile X Mental Retardation ◽  
Mental Retardation Protein

Correction of Fragile X Syndrome in Mice. Dölen G, Osterweil E, Rao BSS, Smith GB, Auerbach BD, Chattarji S, Bear MF. Neuron 2007;56:955–962. Fragile X syndrome (FXS) is the most common form of heritable mental retardation and the leading identified cause of autism. FXS is caused by transcriptional silencing of the FMR1 gene that encodes the fragile X mental retardation protein (FMRP), but the pathogenesis of the disease is unknown. According to one proposal, many psychiatric and neurological symptoms of FXS result from unchecked activation of mGluR5, a metabotropic glutamate receptor. To test this idea we generated Fmr1 mutant mice with a 50% reduction in mGluR5 expression and studied a range of phenotypes with relevance to the human disorder. Our results demonstrate that mGluR5 contributes significantly to the pathogenesis of the disease, a finding that has significant therapeutic implications for fragile X and related developmental disorders. Limbic Epileptogenesis in a Mouse Model of Fragile X Syndrome. Qiu LF, Lu TJ, Hu XL, Yi YH, Liao WP, Xiong ZQ. Cereb Cortex 2009 in press. (doi:10.1093/cercor/bhn163) Fragile X syndrome (FXS), caused by silencing of the Fmr1 gene, is the most common form of inherited mental retardation. Epilepsy is reported to occur in 20–25% of individuals with FXS. However, no overall increased excitability has been reported in Fmr1 knockout (KO) mice, except for increased sensitivity to auditory stimulation. Here, we report that kindling increased the expressions of Fmr1 mRNA and protein in the forebrain of wild-type (WT) mice. Kindling development was dramatically accelerated in Fmr1 KO mice, and Fmr1 KO mice also displayed prolonged electrographic seizures during kindling and more severe mossy fiber sprouting after kindling. The accelerated rate of kindling was partially repressed by inhibiting N-methyl-D-aspartic acid receptor (NMDAR) with MK-801 or mGluR5 receptor with 2-methyl-6-(phenylethynyl)-pyridine (MPEP). The rate of kindling development in WT was not effected by MPEP, however, suggesting that FMRP normally suppresses epileptogenic signaling downstream of metabotropic glutamate receptors. Our findings reveal that FMRP plays a critical role in suppressing limbic epileptogenesis and predict that the enhanced susceptibility of patients with FXS to epilepsy is a direct consequence of the loss of an important homeostatic factor that mitigates vulnerability to excessive neuronal excitation.

Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway

2004 ◽  
Vol 7 (2) ◽  
pp. 113-117 ◽  
Author(s):  
Peng Jin ◽  
Daniela C Zarnescu ◽  
Stephanie Ceman ◽  
Mika Nakamoto ◽  
Julie Mowrey ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Genetic Interaction ◽  
Fragile X ◽  
Fragile X Mental Retardation ◽  
Mental Retardation Protein ◽  
Microrna Pathway

scholarly journals The Fragile X Mental Retardation Protein protects the lung from xenobiotic stress by facilitating the Integrated Stress Response

2021 ◽  
Author(s):  
Deblina Sain Basu ◽  
Rital Bhavsar ◽  
Imtiyaz Gulami ◽  
Saimanoz Lingamallu ◽  
Ravi Muddashetty ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Stress Response ◽  
Stress Responses ◽  
Fragile X ◽  
Air Pollutant ◽  
Environmental Toxicants ◽  
Integrated Stress Response ◽  
Fragile X Mental Retardation ◽  
Mental Retardation Protein

Stress response pathways protect the lung from the damaging effects of environmental toxicants. Here we investigate the role of the Fragile X Mental Retardation Protein (FMRP), a multifunctional protein implicated in stress responses, in the lung. We report that FMRP is expressed in murine and human lungs, in the airways and more broadly. Analysis of airway stress responses in mice and in a murine cell line ex vivo, using the well-established Naphthalene (Nap) injury model, reveals that FMRP-deficient cells exhibit increased expression of markers of oxidative and genotoxic stress and increased cell death. We find that FMRP-deficient cells fail to actuate the Integrated Stress Response Pathway (ISR) and upregulate the transcription factor ATF4. Knockdown of ATF4 expression phenocopies the loss of FMRP. We extend our analysis of the role of FMRP to human bronchial BEAS-2B cells, using a 9, 10-Phenanthrenequinone air pollutant model, to find that FMRP-deficient BEAS-2B also fail to actuate the ISR and exhibit greater susceptibility. Taken together, our data suggest that FMRP has a conserved role in protecting the airways by facilitating the ISR.

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