2017
DOI: 10.1016/j.bbr.2016.10.023
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Abstract: A major aspect of mammalian aging is the decline in functional competence of many self-renewing cell types, including adult-born neuronal precursors. Since age-related senescence of self-renewal occurs simultaneously with chronic up-regulation of the p38MAPKalpha (p38α) signaling pathway, we used the dominant negative mouse model for attenuated p38α activity (DN-p38αAF/+ ) in which Thr180 and Tyr182 are mutated (T→A/Y→F) to prevent phosphorylation activation (DN-p38αAF/+) and kinase activity. As a result, aged… Show more

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Cited by 17 publications
(24 citation statements)
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“…The effect we found on episodic memory is in line with a broad scientific literature that indicates that p38 α in involved in oligomeric amyloid‐beta and inflammation‐induced synaptic dysfunction and to stress‐ and age‐related synaptic dysfunction in the hippocampus 4, 5, 10, 11, 12, 13, 14, 31. In our clinical study, the ES that we saw for immediate and delay recall compares favorably to ES of ≤0.2 for WMS immediate or delayed recall at week 12 in the placebo‐treated subjects in two trials of Souvenaid in a similar patient population (mild AD, baseline MMSE = 24) 32, 33.…”
Section: Discussionsupporting
confidence: 90%
“…The effect we found on episodic memory is in line with a broad scientific literature that indicates that p38 α in involved in oligomeric amyloid‐beta and inflammation‐induced synaptic dysfunction and to stress‐ and age‐related synaptic dysfunction in the hippocampus 4, 5, 10, 11, 12, 13, 14, 31. In our clinical study, the ES that we saw for immediate and delay recall compares favorably to ES of ≤0.2 for WMS immediate or delayed recall at week 12 in the placebo‐treated subjects in two trials of Souvenaid in a similar patient population (mild AD, baseline MMSE = 24) 32, 33.…”
Section: Discussionsupporting
confidence: 90%
“…Both ERK and p38 signaling pathways might contribute to the acceleration in the differentiation process. Previous reports have shown that MAPK signaling pathway is involved in neuronal differentiation (D'Angelo, et al, 2011;Di Loreto et al, 2007) and degeneration (Cortez et al,2017;Liu et al, 2016a;Sun et al, 2017) depending on different cell types and stages. MAPK signaling pathway seems to play dual roles in regulating neuronal functions.…”
Section: Discussionmentioning
confidence: 99%
“…Aberrant mitogen‐activated protein kinase (MAPK) signaling (e.g., ERK, p38, JNK) is found in human AD brains and AD mouse models (Cortez et al, 2017; Savage et al, 2002; Zhu et al, 2000). MAPK signaling plays a crucial role in cell proliferation and differentiation (Harris et al, 2004; Segal and Greenberg, 1996).…”
Section: Introductionmentioning
confidence: 99%
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