Limits...
Alzheimer-related decrease in CYFIP2 links amyloid production to tau hyperphosphorylation and memory loss

View Article: PubMed Central - PubMed

ABSTRACT

CYFIP2 is thought to regulate mRNA translation at synapses. Tiwari et al. reveal reduced CYFIP2 expression in post-mortem Alzheimer’s disease brains, and show that CYFIP2 reduction in mice causes abnormal amyloid production, tau hyperphosphorylation, and spatial memory loss. CYFIP2 could represent a molecular ‘hub’ with potential as a therapeutic target in Alzheimer’s disease.

No MeSH data available.


Related in: MedlinePlus

Reduced CYFIP2 expression does not affect CYFIP1 expression, but leads to increased APP expression at protein but not mRNA level in the hippocampus. (A) Representative western blots. (B) Quantification showed that CYFIP2 expression is reduced by ∼50% in hippocampal synaptosomes of Cyfip2+/− mice (black bar; n = 7) in comparison to wild-type littermates (grey bar, n = 8). CYFIP1 levels are not significantly changed in the same lysates. For quantification CYFIP1 and CYFIP2 expression were normalized to levels of NSE, a neuronal marker. (C) Representative western blots. (D) Quantification showed that APP protein expression is significantly increased ∼2-fold in hippocampal synaptosomes of Cyfip2+/− mice (black bar) in comparison to wild-type littermates (grey bar; n = 8 per genotype). (E) Quantitative PCR analysis showed that App mRNA levels are not elevated in hippocampi of Cyfip2+/− mice (black bar) in comparison to wild-type littermates (grey bar) when normalized to the housekeeping gene Hprt (n = 8 per genotype). Means ± SEM are shown. ***P < 0.001.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5035822&req=5

aww205-F2: Reduced CYFIP2 expression does not affect CYFIP1 expression, but leads to increased APP expression at protein but not mRNA level in the hippocampus. (A) Representative western blots. (B) Quantification showed that CYFIP2 expression is reduced by ∼50% in hippocampal synaptosomes of Cyfip2+/− mice (black bar; n = 7) in comparison to wild-type littermates (grey bar, n = 8). CYFIP1 levels are not significantly changed in the same lysates. For quantification CYFIP1 and CYFIP2 expression were normalized to levels of NSE, a neuronal marker. (C) Representative western blots. (D) Quantification showed that APP protein expression is significantly increased ∼2-fold in hippocampal synaptosomes of Cyfip2+/− mice (black bar) in comparison to wild-type littermates (grey bar; n = 8 per genotype). (E) Quantitative PCR analysis showed that App mRNA levels are not elevated in hippocampi of Cyfip2+/− mice (black bar) in comparison to wild-type littermates (grey bar) when normalized to the housekeeping gene Hprt (n = 8 per genotype). Means ± SEM are shown. ***P < 0.001.

Mentions: We studied the functional impact of reduced CYFIP2 expression in Cyfip2+/− mice. We confirmed earlier work (Kumar et al., 2013) that showed that these mutants have reduced CYFIP2 protein expression by ∼50% in hippocampal synaptosomes in comparison to wild-type littermates (t = 4.90, P < 0.001; Fig. 2A and B) (for specificity of hippocampal synaptosomes, see Supplementary Fig. 6), and ∼40% in total hippocampal lysates (Supplementary Fig. 7A and B). Further, we found that CYFIP1 expression was not altered in hippocampal synaptosomes from CYFIP2+/− mutants in comparison to wild-type littermates (t = 0.13, P > 0.090; Fig. 2A and B). Hence, we showed that CYFIP1 and CYFIP2 expression regulations are not dependent on each other.Figure 2


Alzheimer-related decrease in CYFIP2 links amyloid production to tau hyperphosphorylation and memory loss
Reduced CYFIP2 expression does not affect CYFIP1 expression, but leads to increased APP expression at protein but not mRNA level in the hippocampus. (A) Representative western blots. (B) Quantification showed that CYFIP2 expression is reduced by ∼50% in hippocampal synaptosomes of Cyfip2+/− mice (black bar; n = 7) in comparison to wild-type littermates (grey bar, n = 8). CYFIP1 levels are not significantly changed in the same lysates. For quantification CYFIP1 and CYFIP2 expression were normalized to levels of NSE, a neuronal marker. (C) Representative western blots. (D) Quantification showed that APP protein expression is significantly increased ∼2-fold in hippocampal synaptosomes of Cyfip2+/− mice (black bar) in comparison to wild-type littermates (grey bar; n = 8 per genotype). (E) Quantitative PCR analysis showed that App mRNA levels are not elevated in hippocampi of Cyfip2+/− mice (black bar) in comparison to wild-type littermates (grey bar) when normalized to the housekeeping gene Hprt (n = 8 per genotype). Means ± SEM are shown. ***P < 0.001.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5035822&req=5

aww205-F2: Reduced CYFIP2 expression does not affect CYFIP1 expression, but leads to increased APP expression at protein but not mRNA level in the hippocampus. (A) Representative western blots. (B) Quantification showed that CYFIP2 expression is reduced by ∼50% in hippocampal synaptosomes of Cyfip2+/− mice (black bar; n = 7) in comparison to wild-type littermates (grey bar, n = 8). CYFIP1 levels are not significantly changed in the same lysates. For quantification CYFIP1 and CYFIP2 expression were normalized to levels of NSE, a neuronal marker. (C) Representative western blots. (D) Quantification showed that APP protein expression is significantly increased ∼2-fold in hippocampal synaptosomes of Cyfip2+/− mice (black bar) in comparison to wild-type littermates (grey bar; n = 8 per genotype). (E) Quantitative PCR analysis showed that App mRNA levels are not elevated in hippocampi of Cyfip2+/− mice (black bar) in comparison to wild-type littermates (grey bar) when normalized to the housekeeping gene Hprt (n = 8 per genotype). Means ± SEM are shown. ***P < 0.001.
Mentions: We studied the functional impact of reduced CYFIP2 expression in Cyfip2+/− mice. We confirmed earlier work (Kumar et al., 2013) that showed that these mutants have reduced CYFIP2 protein expression by ∼50% in hippocampal synaptosomes in comparison to wild-type littermates (t = 4.90, P < 0.001; Fig. 2A and B) (for specificity of hippocampal synaptosomes, see Supplementary Fig. 6), and ∼40% in total hippocampal lysates (Supplementary Fig. 7A and B). Further, we found that CYFIP1 expression was not altered in hippocampal synaptosomes from CYFIP2+/− mutants in comparison to wild-type littermates (t = 0.13, P > 0.090; Fig. 2A and B). Hence, we showed that CYFIP1 and CYFIP2 expression regulations are not dependent on each other.Figure 2

View Article: PubMed Central - PubMed

ABSTRACT

CYFIP2 is thought to regulate mRNA translation at synapses. Tiwari et al. reveal reduced CYFIP2 expression in post-mortem Alzheimer&rsquo;s disease brains, and show that CYFIP2 reduction in mice causes abnormal amyloid production, tau hyperphosphorylation, and spatial memory loss. CYFIP2 could represent a molecular &lsquo;hub&rsquo; with potential as a therapeutic target in Alzheimer&rsquo;s disease.

No MeSH data available.


Related in: MedlinePlus