Upregulation and antiapoptotic role of endogenous Alzheimer amyloid precursor protein in dorsal root ganglion neurons

Nishimura, Isao; Takazaki, Risa; Kuwako, Ken-ichiro; Enokido, Yasushi; Yoshikawa, Kunio

doi:10.1016/s0014-4827(03)00066-1

Cited by 23 publications

(16 citation statements)

References 55 publications

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“…Previously, APP expression was shown to increase in response to cell death (Nishimura et al 2003), where it is thought to serve a neuroprotective function (Lesort et al 1997;Kinoshita et al 2002). Other studies report that traumatic brain injury can induce expression of APP (Pierce et al 1996;Murakami et al 1998;Ciallella et al 2002).…”

Section: Discussionmentioning

confidence: 99%

MCP-1-Induced Migration of NT2 Neuroprogenitor Cells Involving APP Signaling

Vrotsos

Sugaya

2008

Cell Mol Neurobiol

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Neuroprogenitor cells are an important resource because of their great potential to replace damaged cells in the brain caused by trauma and disease. Studies have shown that when neuroprogenitor cells are transplanted into the brain they migrate towards damaged areas, suggesting that these areas express factors that recruit migrating cells. Generally, after neuronal injury, there is a neuroinflammatory response that results in increased chemokine production. In this present study, we demonstrate that monocyte chemoattractant protein-1 (MCP-1) significantly induces the migration of NT2 neuroprogenitor cells. Activation of intracellular cyclic adenosine monophosphate or protein kinase C with forskolin and phorbol 12-myristate 13-acetate, respectively, was able to completely abolish the MCP-1-induced migration. Contrarily, neither extracellular signal-regulated kinase nor p38 mitogen-activated protein kinase was required for NT2 cells to respond to MCP-1. Previously, we showed that amyloid precursor protein (APP) activity increases MCP-1 expression in NT2 cells. We now demonstrate that NT2 cells expressing APP can induce migration of other neuroprogenitor cells. Utilizing a MCP-1 neutralizing antibody, we discovered that APP-induced migration was not caused solely by increased MCP-1 production. Interestingly, APP-increased expression of several C-C chemokines: MCP-1, regulated upon activation, normal T-cell expressed, and secreted (RANTES), and macrophage inflammatory protein alpha (MIP-1 alpha). This demonstrates the unique role APP has in regulating chemokine production, which directly affects cell migration. Taken together, these data provides greater detail of the chemotactic factors and intracellular signaling that direct neuroprogenitor cell migration, allowing for better understanding of cell migration during transplantation.

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Section: Discussionmentioning

confidence: 99%

MCP-1-Induced Migration of NT2 Neuroprogenitor Cells Involving APP Signaling

Vrotsos

Sugaya

2008

Cell Mol Neurobiol

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“…APP and its derivatives (formed by secretase processing) are expressed in the developing CNS, where they have multiple functions and have been associated with pathological processes such as Alzheimer's disease (reviewed in Dodart et al, 2000;Panegyres, 2001). In addition to cell adhesion properties, APP is important for cell viability and neuroprotection (Goodman and Mattson, 1994;Perez et al, 1997;Nishimura et al, 2003). APP is involved in the morphological and functional plasticity of nerve cells (reviewed in Dodart et al, 2000) and has also been implicated in cell signaling pathways (Mook-Jung and Saitoh, 1997;Russo et al, 2002;reviewed in Mattson and Furukawa, 1998).…”

Section: Cell Adhesionmentioning

confidence: 99%

Hox Genes and Their Candidate Downstream Targets in the Developing Central Nervous System

Akin

Nazarali

2005

Cell Mol Neurobiol

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1. Homeobox (Hox) genes were originally discovered in the fruit fly Drosophila, where they function through a conserved homeodomain as transcriptional regulators to control embryonic morphogenesis. Since then over 1000 homeodomain proteins have been identified in several species. In vertebrates, 39 Hox genes have been identified as homologs of the original Drosophila complex, and like their Drosophila counterparts they are organized within chromosomal clusters. Vertebrate Hox genes have also been shown to play a critical role in embryonic development as transcriptional regulators. 2. Both the Drosophila and vertebrate Hox genes have been shown to interact with various cofactors, such as the TALE homeodomain proteins, in recognition of consensus sequences within regulatory elements of their target genes. These protein-protein interactions are believed to contribute to enhancing the specificity of target gene recognition in a cell-type or tissue- dependent manner. The regulatory activity of a particular Hox protein on a specific regulatory element is highly variable and dependent on its interacting partners within the transcriptional complex. 3. In vertebrates, Hox genes display spatially restricted patterns of expression within the developing CNS, both along the anterioposterior and dorsoventral axis of the embryo. Their restricted gene expression is suggestive of a regulatory role in patterning of the CNS, as well as in cell specification. Determining the precise function of individual Hox genes in CNS morphogenesis through classical mutational analyses is complicated due to functional redundancy between Hox genes. 4. Understanding the precise mechanisms through which Hox genes mediate embryonic morphogenesis requires the identification of their downstream target genes. Although Hox genes have been implicated in the regulation of several pathways, few target genes have been shown to be under their direct regulatory control. Development of methodologies used for the isolation of target genes and for the analysis of putative targets will be beneficial in establishing the genetic pathways controlled by Hox factors. 5. Within the developing CNS various cell adhesion molecules and signaling molecules have been identified as candidate downstream target genes of Hox proteins. These targets play a role in processes such as cell migration and differentiation, and are implicated in contributing to neuronal processes such as plasticity and/or specification. Hence, Hox genes not only play a role in patterning of the CNS during early development, but may also contribute to cell specification and identity.

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“…SSEPs are thought to reflect conduction through the medial lemniscus and therefore our findings are consistent with abnormalities in the projections arising from the dorsal root ganglion or their rostral extension from the nuclei cuneatus and gracilis in the medulla. Though upregulation of APP has been described in the dorsal root ganglion(Nishimura et al, 2003) such conduction abnormalities have not, to our knowledge, been described in LOAD and therefore may represent an effect of the A431E PSEN1 mutation independent of APP processing. Note that in the one neuropathological report in which the lemniscal pathways were described in a patient with PSEN1 -related SP, no gross abnormalities were seen(Rudzinski, Fletcher, 2008) and SSEPs were described as being normal in the subject with spastic paraparesis imaged with tau PET in the study of Lyoo et al(Lyoo, Cho, 2016).…”

Section: Discussionmentioning

confidence: 79%

Widespread white matter and conduction defects in PSEN1-related spastic paraparesis

Soosman

Joseph‐Mathurin

Braskie

et al. 2016

Neurobiology of Aging

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The mechanisms underlying PSEN1 mutation-associated spastic paraparesis (SP) are not clear. We compared diffusion and volumetric magnetic resonance measures between 3 persons with SP associated with the A431E mutation and 7 symptomatic persons with PSEN1 mutations without SP matched for symptom duration. We performed amyloid imaging and central motor and somatosensory conduction studies in one subject with SP. We found decreases in fractional anisotropy and increases in mean diffusivity in widespread white matter areas including the corpus callosum, occipital, parietal, and frontal lobes in PSEN1 mutation carriers with SP. Volumetric measures were not different and amyloid imaging showed low signal in sensorimotor cortex and other areas in a single subject with SP. Electrophysiological studies demonstrated both slowed motor and sensory conduction in the lower extremities in this same subject. Our results suggest that SP in carriers of the A431E PSEN1 mutation is a manifestation of widespread white matter abnormalities not confined to the corticospinal tract that is at most indirectly related to the mutation’s effect on APP processing and amyloid deposition.

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Upregulation and antiapoptotic role of endogenous Alzheimer amyloid precursor protein in dorsal root ganglion neurons

Cited by 23 publications

References 55 publications

MCP-1-Induced Migration of NT2 Neuroprogenitor Cells Involving APP Signaling

MCP-1-Induced Migration of NT2 Neuroprogenitor Cells Involving APP Signaling

Hox Genes and Their Candidate Downstream Targets in the Developing Central Nervous System

Widespread white matter and conduction defects in PSEN1-related spastic paraparesis

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