The AKT1
genotype could be a potential schizophrenia susceptibility gene.

 

Emamian,
Hall, Birnbaum, Karayiorgou and Gogos (2004) showed that the pathogenesis of
schizophrenia were provided by AKT1 signaling pathway. They used several
variations of kinases that were implicated in synaptic plasticity that are
expressed in various cell types such as peripheral blood lymphoctes. Their
first results showed that individuals with schizophrenia had 68% lower levels
of AKT1 kinases than controls, in contrast with the other protein kinases. They
found reduced AKT1 levels in the frontal cortex and lymphocytes in
schizophrenia patients. Second, they found 5 SNPs of the AKT1 locus in 268
families (a total of 335 schizophrenia patients) that were associated with
schizophrenia. These 5 SNPs markers were also associated with frontostriatal
dopaminergic system in healthy individuals by Tan et al. (2008). They found
that genetic variation of AKT1 may be linked to dopamine-associated prefrontal
cortical function and structure. They found the strongest association with
frontal lobe function with the A allele of the AKT1 SNP rs1130233. To measure
the cortical structural and functional changes in DA signaling, the subjects
had to perform a task (which is linked to cortical DA function) while undergoing
functional magnetic resonance imaging scanner (fMRI). They found that carriers of
the A allele had reduced information processing in the PFC. On top of that,
carriers had also reduced gray-matter volume in the right PFC and the caudate
nucleus.  Besides the AKT1 gene that has
been associated with schizophrenia there are more genes, like the
dystrobrevin-binding protein 1 (DTNBP1). Dysbindin is believed to play a role
in synaptic plasticity and signal transduction. Numakawa et al. (2004) showed
that the phosphorylation levels of AKT were suppressed by the downregulation of
dysbindin expression. They examined the neurotrophic effect through AKT
signaling pathway as a function of dysbindin. They showed that overexpression
of dysbindin resulted in activation of AKT. A PI3 kinase inhibitor, LY294002, inhibited
the activation of AKT by the overexpression of dysbindin. Their data implicates
that AKT signaling in schizophrenia patients might be caused by reduced
expression of dysbindin.

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