Decreased Expression of Hippocampal Cholinergic Neurostimulating Peptide Precursor Protein mRNA in the Hippocampus in Alzheimer Disease

Maki, Mina; Matsukawa, Noriyuki; Yuasa, Hiroyuki; Otsuka, Yasushi; Yamamoto, Takayuki; Akatsu, Hiroyasu; Okamoto, Takashi; Ueda, Ryuzo; Ojika, Kosei

doi:10.1093/jnen/61.2.176

Cited by 78 publications

(62 citation statements)

References 46 publications

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“…63 Consistent with a potential role of HCNP in AD, levels of pebp1 mRNA are suppressed in the CA1 region of the hippocampi of clinically late-onset AD patients relative to nondemented controls. 64 Given previous evidence that shows that AD pathologies are localized in the CA1 region and there is loss of cholinergic fibers innervating the hippocampus, this study suggests that reduced expression of HCNP may contribute to the pathogenesis of AD. In comparison, earlier work showed that the cerebrospinal fluid (CSF) of some early-onset, but not late-onset, AD patients exhibits high levels of HCNP relative to non-AD patients.…”

Section: Rkip and Association With Alzheimer's Diseasesupporting

confidence: 63%

Raf Kinase Inhibitory Protein (RKIP): Functional Pleiotropy in the Mammalian Brain

et al. 2014

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In 1984, a cytosolic protein was isolated from bovine brain and coined phosphatidylethanolamine binding protein (PEBP) to describe its phospholipid-binding potential. Its cellular function remained elusive for more than a decade until it was discovered that PEBP had the ability to suppress the Raf1-mitogen activated protein kinase (MAPK) pathway, earning it the new name of Raf1 kinase inhibitory protein (RKIP). This milestone discovery has paved the way for numerous studies that have now extended the reach of RKIP's function to other signaling cascades, within the context of various physiological and pathophysiological systems. This review will summarize our current knowledge of the neurophysiological roles of RKIP in the mammalian brain, including its function in the circadian clock and synaptic plasticity. It will also discuss evidence for an involvement of RKIP and its derived neuropeptide, hippocampal cholinergic neurostimulating peptide (HCNP), in neural development and differentiation. Implications in certain pathologies such as Alzheimer's disease and brain cancer will be highlighted. By chronicling the diverse functions of RKIP in the brain, we hope that this review will serve as a timely resource that ignites future studies on this versatile, multifaceted protein in the nervous system.

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Section: Rkip and Association With Alzheimer's Diseasesupporting

confidence: 63%

Raf Kinase Inhibitory Protein (RKIP): Functional Pleiotropy in the Mammalian Brain

et al. 2014

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“…The role of RKIP-1 in AD emerges through its diminished expression in affected neurons [14]. An inverse correlation between the severity of AD and the RKIP-1 level in human and mouse brains has been reported [14,24].…”

Section: Discussionmentioning

confidence: 99%

Raf kinase inhibitory protein knockout mice: Expression in the brain and olfaction deficit

Theroux

Pereira

Casten

et al. 2007

Brain Research Bulletin

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Raf Kinase Inhibitory Protein (RKIP-1) is involved in the regulation of the MAP kinase, NF-κB, and GPCR signaling pathways. It is expressed in numerous tissues and cell types and orthologues have been documented throughout the animal and plant kingdoms. RKIP-1 has also been reported as an inhibitor of serine proteases, and a precursor of a neurostimulatory peptide. RKIP-1 has been implicated as a suppressor of metastases in several human cancers. We generated a knockout strain of mice to further assess RKIP-1's function in mammals. RKIP-1 is expressed in many tissues with the highest protein levels detectable in testes and brain. In the brain, expression was ubiquitous in limbic formations, and homozygous mice developed olfaction deficits in the first year of life. We postulate that RKIP-1 may be a modulator of behavioral responses.

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“…For example, RKIP has a variety of physiological functions in brain, including its function in the synaptic plasticity and circadian clock [3]. As a precursor protein of hippocampal cholinergic neurons, RKIP is important to synthesis acetylcholine and develop septal cholinergic neurons for learning and memory [4]. Furthmore, RKIP expression disorders can lead to diabetic nephropathy and Alzheimer’s disease [5].…”

Section: Introductionmentioning

confidence: 99%

Raf Kinase Inhibitor Protein Attenuates Ischemic-Induced Microglia Cell Apoptosis and Activation Through NF-κB Pathway

Zhang

Chen

et al. 2017

Cell Physiol Biochem

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Background: Acute ischemic stroke is one of the most important factors leading to disability and death with the characterization of accumulated neuron death and injured supportive neurovascular structures. Raf-1 kinase inhibitory protein (RKIP) is a key molecule in cell response to survival or death stimuli. However, the role of RKIP in stroke is worthy to be further studied. Methods: We used lentivirus mediated RKIP knockdown and overexpression to investigate the effect of RKIP on animal models of focal cerebral ischemia. Cell Counting Kit-8 assay, lactate dehydrogenase release analysis, and Annexin V-APC apoptosis assay were used to detect the effect RKIP on microglial cell apoptosis and survival. Transwell migration assay was carried out to evaluate the migration of microglia cells. The releases of inflammatory cytokines were determined by ELISA. The activation of NF-kappaB signaling pathway was determined by western blot. Results: Overexpression of RKIP reduced focal cerebral ischemia injury. RKIP knockdown and overexpression regulated survival, activation, and motility via the NF-κB pathway. NF-κB inhibitor BAY 11-7082 blocked the changes caused by RKIP down-regulation after oxygen-glucose deprivation (OGD). RKIP overexpression inhibited the upregulation of phosphorylation of NF-κB induced by OGD and cerebral ischemia. Conclusions: The present study showed that RKIP protects against ischemic stroke through inhibition of microglial excessive activation, inhibits its motility, and promotes neuronal survival partly though IKKβ-IκBα-NF-κB signaling axis and indicate that RKIP is a new target for the treatment of ischemic stroke.

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Decreased Expression of Hippocampal Cholinergic Neurostimulating Peptide Precursor Protein mRNA in the Hippocampus in Alzheimer Disease

Cited by 78 publications

References 46 publications

Raf Kinase Inhibitory Protein (RKIP): Functional Pleiotropy in the Mammalian Brain

Raf Kinase Inhibitory Protein (RKIP): Functional Pleiotropy in the Mammalian Brain

Raf kinase inhibitory protein knockout mice: Expression in the brain and olfaction deficit

Raf Kinase Inhibitor Protein Attenuates Ischemic-Induced Microglia Cell Apoptosis and Activation Through NF-κB Pathway

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