fragile-x syndrome (fmrp)

8/11/2019 Fragile-X Syndrome (FMRP)

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FMRP (Fragile X Mental Retardation Protein)


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Fragile X syndrome is caused by the loss ofproduction of Fragile X Mental Retardation

Protein (FMRP) in response to the FMR 1 genesilencing.

BUTWhy we cant just feed a person with Fragile X

syndrome with more protein or injected him withlots of FMRP ?


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Is a kind of specific protein and not a generalprotein

Present in many tissues, including brain,testes and ovaries

It needs to be present in the right cells at theright time in the right amount to carry out itsfunction optimally (Example: Fragile X

syndrome is due to the loss of FMRP in brain)


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Begins in nucleus when DNA receives arequest of the specific information

DNA transcribes the coded information

The copy of DNA is known as mRNA mRNA leaves the nucleus and goes to

cytoplasm

The coded mRNA is translated on the

ribosome with the help of tRNA FMRP is formed


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A brain expression analysis was done on amonkey and it shows that certain brainstructures display high FMRP levels, such ascerebellum and temporal lobe structures.

This supports that the FMRP expression lossis linked to the behaviourial and congnitive

impairment associated with these structures


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Plays important role in development ofconnections between nerve cells (synapses),where cell to cell communication occurs

Plays an important role in mGluR-mediatedplasticity

Maintains the balance between how brainstrengthens or eliminates connections betweenneurons

Acts as a shuttle within cells by transportingmolecules called mRNA

Controls instruction in mRNA as to buildproteins for the functioning of nerves


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FMRP in nerves located to the dendrite near

dendritic spines These protusions from the dendrite represent

morphologically and functionally specializedpost-synaptic structures, which undergodramatic proliferative and regressive changesduring brain development, learning andmemory function

FMRP directly regulates the synapse numberpostnatally through postsynaptic interactionswith RNA and regulation of translation


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Ability of synapses to strengthen or weakenover time, in response to increases anddecreases in their activities

One of the important neurochemicalfoundations of learning and memory

Can be divided into short term plasticity andlong term plasticity depends on the time

scales


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SynapticPlasticity

Long Term

Long Term

Depression

Long Term

Potentiation

Short Term


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Defective adult neurogenesis may contributeto learning impairment

Unregulated activation of mGluR Long TermDepression which results in the inability ofbrain to maintain strong synapses requiredfor learning and memory

Absence of FMRP will increase the translation

of synaptic mRNA leading to the upregulationof proteins that influence the synapticfunction and plasticity


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Leads to excessive action potentialbroadening during repetitive activity,enhanced presynaptic calcium influx and

elevated neurotransmitter release whichcauses degradation of synaptic informationtransmission

Affects both presynaptic and postsynapticfunctions which lead to defects in synapticinformation transmission

Represses mRNA production and protein

synthesis which leads to exaggerated LTD


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Affects the dopamine pathways in theprefrontal cortex which result in attentiondifficulty, hyperactivity and impulse control

problems associated with the Fragile Xsyndrome

Downregulation of GABA pathways, whichserve as an inhibitory function and areinvolved in learning and memory

fragile-x syndrome (fmrp)

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