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
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
transient cerebral ischemia  ISOFmr1 (Rattus norvegicus)11566024; 11566024mRNA and protein:increased expression:striatum (rat)RGD 
transient cerebral ischemia  IEP 11566024mRNA and protein:increased expression:striatum (rat)RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

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