FMRP (Fragile X Mental Retardation Protein)

Fragile X syndrome is caused by the loss of

production of Fragile X Mental Retardation
Protein (FMRP) in response to the FMR 1 gene
silencing.

BUT
Why we cant just feed a person with Fragile X
syndrome with more protein or injected him with
lots of FMRP ?
Is a kind of specific protein and not a general
protein
Present in many tissues, including brain,
testes and ovaries
It needs to be present in the right cells at the
right time in the right amount to carry out its
function optimally (Example: Fragile X
syndrome is due to the loss of FMRP in brain)

Begins in nucleus when DNA receives a
request 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
A brain expression analysis was done on a
monkey and it shows that certain brain
structures display high FMRP levels, such as
cerebellum and temporal lobe structures.

This supports that the FMRP expression loss
is linked to the behaviourial and congnitive
impairment associated with these structures
Plays important role in development of
connections between nerve cells (synapses),
where cell to cell communication occurs
Plays an important role in mGluR-mediated
plasticity
Maintains the balance between how brain
strengthens or eliminates connections between
neurons
Acts as a shuttle within cells by transporting
molecules called mRNA
Controls instruction in mRNA as to build
proteins for the functioning of nerves
FMRP in nerves located to the dendrite near
dendritic spines
These protusions from the dendrite represent
morphologically and functionally specialized
post-synaptic structures, which undergo
dramatic proliferative and regressive changes
during brain development, learning and
memory function
FMRP directly regulates the synapse number
postnatally through postsynaptic interactions
with RNA and regulation of translation

Ability of synapses to strengthen or weaken
over time, in response to increases and
decreases in their activities
One of the important neurochemical
foundations of learning and memory
Can be divided into short term plasticity and
long term plasticity depends on the time
scales

Synaptic
Plasticity
Long Term
Long Term
Depression
Long Term
Potentiation
Short Term
Defective adult neurogenesis may contribute
to learning impairment
Unregulated activation of mGluR Long Term
Depression which results in the inability of
brain to maintain strong synapses required
for learning and memory
Absence of FMRP will increase the translation
of synaptic mRNA leading to the upregulation
of proteins that influence the synaptic
function and plasticity

Leads to excessive action potential
broadening during repetitive activity,
enhanced presynaptic calcium influx and
elevated neurotransmitter release which
causes degradation of synaptic information
transmission
Affects both presynaptic and postsynaptic
functions which lead to defects in synaptic
information transmission
Represses mRNA production and protein
synthesis which leads to exaggerated LTD

Affects the dopamine pathways in the
prefrontal cortex which result in attention
difficulty, hyperactivity and impulse control
problems associated with the Fragile X
syndrome
Downregulation of GABA pathways, which
serve as an inhibitory function and are
involved in learning and memory