RGD Reference Report - Positive feedback regulation of Akt-FMRP pathway protects neurons from cell death. - Rat Genome Database

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Positive feedback regulation of Akt-FMRP pathway protects neurons from cell death.

Authors: Jeon, SJ  Han, SH  Yang, SI  Choi, JW  Kwon, KJ  Park, SH  Kim, HY  Cheong, JH  Ryu, JH  Ko, KH  Wells, DG  Shin, CY 
Citation: Jeon SJ, etal., J Neurochem. 2012 Oct;123(2):226-38. doi: 10.1111/j.1471-4159.2012.07886.x. Epub 2012 Aug 22.
RGD ID: 11566024
Pubmed: PMID:22817682   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1471-4159.2012.07886.x   (Journal Full-text)

J. Neurochem. (2012) 123, 226-238. ABSTRACT: Fragile X syndrome (FXS), the most common single genetic cause of mental retardation and autistic spectrum disease, occurs when FMR1 gene is mutated. FMR1 encodes fragile X mental retardation protein (FMRP) which regulates translation of mRNAs playing important roles in the development of neurons as well as formation and maintenance of synapses. To examine whether FMRP regulates cell viability, we induced apoptosis in rat primary cortical neurons with glutamate in vitro and with middle cerebral artery occlusion (MCAO) in striatal neurons in vivo. Both conditions elicited a rapid, but transient FMRP expression in neurons. This up-regulated FMRP expression was abolished by pre-treatment with PI3K and Protein Kinase B (Akt) inhibitors: LY294002, Akt inhibitor IV, and VIII. Reduced FMRP expression in vitro or in vivo using small hairpin Fmr1 virus exacerbated cell death by glutamate or MCAO, presumably via hypophosphorylation of Akt and reduced expression of B-cell lymphoma-extra large (Bcl-xL). However, over-expression of FMRP using enhanced green fluorescent protein (eGFP)-FMRP constructs alleviated cell death, increased Akt activity, and enhanced Bcl-xL production. The pro-survival role of Akt-dependent up-regulation of FMRP in glutamate-stimulated cultured neuron as well as in ischemic brain may have a clinical importance in FXS as well as in neurodegenerative disorders and traumatic brain injury.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FMR1Humantransient cerebral ischemia  ISORGD:2623mRNA, protein:increased expression:striatum (rat)RGD 
Fmr1Rattransient cerebral ischemia  IEP mRNA, protein:increased expression:striatum (rat)RGD 
Fmr1Mousetransient cerebral ischemia  ISORGD:2623mRNA, protein:increased expression:striatum (rat)RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Fmr1Ratcellular response to L-glutamate  IEP  RGD 
Fmr1Ratnegative regulation of neuron apoptotic process  IMP  RGD 
Fmr1Ratnegative regulation of protein processing  IMP Casp3RGD 
Fmr1Ratpositive regulation of gene expression  IMP Bcl2l1RGD 
Fmr1Ratpositive regulation of protein phosphorylation  IMP PI3K, Akt1RGD 

Objects Annotated

Genes (Rattus norvegicus)
Fmr1  (fragile X messenger ribonucleoprotein 1)

Genes (Mus musculus)
Fmr1  (fragile X messenger ribonucleoprotein 1)

Genes (Homo sapiens)
FMR1  (fragile X messenger ribonucleoprotein 1)


Additional Information