Overexpression of NMDAR2B in an inflammatory model of Alzheimer's disease: Modulation by NOS inhibitors

Maher, Ahmed; Sayed, Nesrine S. El; Breitinger, Hans‐Georg

doi:10.1016/j.brainresbull.2014.10.007

Cited by 31 publications

(18 citation statements)

References 45 publications

(48 reference statements)

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“…Unlike our in vitro experiments, these results suggest the possibility of no participation of NOS in vivo. However, it was reported that NOS inhibitors of nNOS, inducible NOS (iNOS), and eNOS had favorable effects on cognitive function in several AD mouse models (Maher et al, 2014;Santhanam et al, 2015). Given the differences observed in vivo and in vitro, because nNOS expression is naturally downregulated in the hippocampus of SAMP8 (Han et al, 2010), it could be difficult to evaluate the effect of nNOS as shown in vitro.…”

Section: Discussionmentioning

confidence: 97%

Protective effects of NMDA receptor antagonist, memantine, against senescence of PC12 cells: A possible role of nNOS and combined effects with donepezil

Ota

Ogawa

Ouchi

et al. 2015

Experimental Gerontology

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Section: Discussionmentioning

confidence: 97%

Protective effects of NMDA receptor antagonist, memantine, against senescence of PC12 cells: A possible role of nNOS and combined effects with donepezil

Ota

Ogawa

Ouchi

et al. 2015

Experimental Gerontology

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“…In the case of trehalose, L-NAME and carbamazepine, several studies show that their therapeutic effects in AD models are concomitantly accompanied by autophagy induction (Kruger et al, 2012;Pierzynowska et al, 2018;Sarkar, 2013); However, a mechanistic link between these observations was not demonstrated. In this context, it should be noted that L-NAME is a well-known inhibitor of nitric oxide synthase, which could be negatively involved in AD-associated neuroinflammation (Maher, El-Sayed, Breitinger, & Gad, 2014), and that the effect of trehalose in AD was suggested to be mediated by its direct interaction with tau and Aβ (Kruger et al, 2012;Liu, Barkhordarian, Emadi, Park, & Sierks, 2005). Indeed, Portbury et al (2017) reported that the beneficial effects of trehalsoe in the Tg2576 mouse model of AD were independent of autophagy induction.…”

Section: Evaluating the Role Of Autophagy Induction In Ad: Open Quementioning

confidence: 99%

Autophagy induction in the treatment of Alzheimer's disease

Schmukler

Pinkas‐Kramarski

2019

Drug Development Research

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A growing body of evidence indicates that autophagy, an intracellular degradation pathway, profoundly affects Alzheimer's disease (AD) pathogenesis. Autophagy mediates the degradation of neurotoxic material and damaged organelles, allowing their clearance by glial and neuronal cells, while impaired autophagy may account for the accumulation of protein aggregates. Accordingly, dysfunctional autophagy is one of AD hallmarks; it occurs early in the disease development, which makes it an attractive therapeutic intervention target. Therefore, in recent years, the potential of autophagy induction as a treatment for AD has been studied extensively using various autophagy inducers, most of which are already in clinical practice for other medical conditions. Albeit promising results, including in AD clinical trials, this therapeutic strategy still requires careful consideration in order to fully understand the role of autophagy in AD pathogenesis and to further improve the outcomes. This review summarizes the current findings in this field and raises open questions and new prospects.

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“…Accumulating evidence has demonstrated that recruitment of the Ca 2? -dependent enzyme nNOS via PSD95 is a key contributor to neuronal dysfunction [19][20][21][22][23][24]. Our result showed that interaction of APPL1 with PSD95 through the PDZ2 domain results in activation of the neuroprotective Akt pathway.…”

Section: Appl1 S707a Disrupts Synaptic Activity-mediated Activation Omentioning

confidence: 87%

Serine 707 of APPL1 is Critical for the Synaptic NMDA Receptor-Mediated Akt Phosphorylation Signaling Pathway

Wang

Chen

et al. 2016

Neurosci. Bull.

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Accumulating evidence indicates that the synaptic activation of N-methyl-D-aspartate receptors (NMDARs) has a neuroprotective effect on neurons. Our previous study demonstrated that APPL1 (adaptor protein containing pleckstrin homology domain, phosphotyrosinebinding domain, and leucine zipper motif) mediates the synaptic activity-dependent activation of PI3K-Akt signaling via coupling this pathway with NMDAR-PSD95 (postsynaptic density protein 95) complexes. However, the molecular mechanism underlying this process is still unknown. In the present study, we investigated the interaction of APPL1 with PSD95 using co-immunocytochemical staining and western blotting. We found that the PDZ2 domain of PSD95 is a binding partner of APPL1. Furthermore, we identified serine 707 of APPL1, a predicted phosphorylation site within the PDZ-binding motif at the C-terminus, as critical for the binding of APPL1 to PSD95, as well as for activation of the Akt signaling pathway during synaptic activity. This suggests that serine 707 of APPL1 is a potential phosphorylation site and may be involved in regulating the neuroprotective Akt signaling pathway that depends on synaptic NMDAR activity.

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Overexpression of NMDAR2B in an inflammatory model of Alzheimer's disease: Modulation by NOS inhibitors

Cited by 31 publications

References 45 publications

Protective effects of NMDA receptor antagonist, memantine, against senescence of PC12 cells: A possible role of nNOS and combined effects with donepezil

Protective effects of NMDA receptor antagonist, memantine, against senescence of PC12 cells: A possible role of nNOS and combined effects with donepezil

Autophagy induction in the treatment of Alzheimer's disease

Serine 707 of APPL1 is Critical for the Synaptic NMDA Receptor-Mediated Akt Phosphorylation Signaling Pathway

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