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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