Presynaptic and Postsynaptic Interaction of the Amyloid Precursor Protein Promotes Peripheral and Central Synaptogenesis

Wang, Zilai; Wang, Baiping; Yang, Li; Guo, Qinxi; Aithmitti, Nadia; Songyang, Zhou; Zheng, Hui

doi:10.1523/jneurosci.2132-09.2009

Cited by 211 publications

(284 citation statements)

References 48 publications

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“…A growing number of studies have documented abnormal electrical activity in APP-transgenic models for Alzheimer's disease (Lalonde et al, 2005;Palop et al, 2007;Westmark et al, 2008;Minkeviciene et al, 2009;Ziyatdinova et al, 2011;Corbett et al, 2013). These models differ in the APP mutations they encode, the coexpressed transgenes, and the promoters used to drive expression.…”

Section: Tet-off App Mice Display Eeg Abnormalities Similar To Other mentioning

confidence: 99%

“…Because the tet-off APP mice exhibit spontaneous EEG abnormalities, we wanted to test whether they were also more vulnerable to chemically induced seizures, as demonstrated for other APPtransgenic models (Del Vecchio et al, 2004;Palop et al, 2007;Westmark et al, 2008). We implanted APP/TTA and control animals with transmitters at 6 -7 months of age to monitor the seizure induction both electrographically and behaviorally.…”

Section: Increased Susceptibility To Chemically Induced Seizures Is Nmentioning

confidence: 99%

“…Spontaneous seizures and sharp wave discharges (SWDs) have been observed in several transgenic models expressing mutations in amyloid precursor protein (APP). The seizure phenotype is most often noted in models carrying the Swedish mutation, including Tg2576 (Westmark et al, 2008), APP23 (Lalonde et al, 2005), hAPPJ20 (Palop et al, 2007;Corbett et al, 2013), and APP/PS1dE9 (Minkeviciene et al, 2009;Ziyatdinova et al, 2011). The prominent amyloid phenotype of these models has pointed to amyloid ␤ (A␤) as the mechanistic link connecting AD with seizures (Palop and Mucke, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…Many AD mouse models also produce high levels of APP, making it difficult to distinguish whether A␤ is solely responsible for seizure activity or if other APP fragments may also contribute. Moreover, unlike most AD patients, transgenic mice overexpress APP during cortical development, when the protein's synaptogenic properties may have unanticipated effects on circuit connectivity (YoungPearse et al, 2008;Wang et al, 2009;Zheng and Koo, 2011). Because of their intrinsic relationship, separating the impact of APP from that of A␤ and amyloid has been experimentally challenging.…”

Section: Introductionmentioning

confidence: 99%

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Genetic Suppression of Transgenic APP Rescues Hypersynchronous Network Activity in a Mouse Model of Alzeimer's Disease

Born¹,

Kim²,

et al. 2014

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Alzheimer's disease (AD) is associated with an elevated risk for seizures that may be fundamentally connected to cognitive dysfunction. Supporting this link, many mouse models for AD exhibit abnormal electroencephalogram (EEG) activity in addition to the expected neuropathology and cognitive deficits. Here, we used a controllable transgenic system to investigate how network changes develop and are maintained in a model characterized by amyloid ␤ (A␤) overproduction and progressive amyloid pathology. EEG recordings in tet-off mice overexpressing amyloid precursor protein (APP) from birth display frequent sharp wave discharges (SWDs). Unexpectedly, we found that withholding APP overexpression until adulthood substantially delayed the appearance of epileptiform activity. Together, these findings suggest that juvenile APP overexpression altered cortical development to favor synchronized firing. Regardless of the age at which EEG abnormalities appeared, the phenotype was dependent on continued APP overexpression and abated over several weeks once transgene expression was suppressed. Abnormal EEG discharges were independent of plaque load and could be extinguished without altering deposited amyloid. Selective reduction of A␤ with a ␥-secretase inhibitor has no effect on the frequency of SWDs, indicating that another APP fragment or the full-length protein was likely responsible for maintaining EEG abnormalities. Moreover, transgene suppression normalized the ratio of excitatory to inhibitory innervation in the cortex, whereas secretase inhibition did not. Our results suggest that APP overexpression, and not A␤ overproduction, is responsible for EEG abnormalities in our transgenic mice and can be rescued independently of pathology.

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Section: Tet-off App Mice Display Eeg Abnormalities Similar To Other mentioning

confidence: 99%

Section: Increased Susceptibility To Chemically Induced Seizures Is Nmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Genetic Suppression of Transgenic APP Rescues Hypersynchronous Network Activity in a Mouse Model of Alzeimer's Disease

Born¹,

Kim²,

et al. 2014

Self Cite

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“…APP can participate in transmembrane signaling events due to its highly conserved extracellular and intracellular domains, which plays important roles in many physiological processes [3][4][5][6][7]. Many recent studies have indicated that APP is overexpressed commonly in solid tumors and mainly involved in promoting proliferation of tumor cells, including oral squamous cell carcinoma [8], pancreatic cancer cells [9], parathyroid tumor [10], and breast cancer [11].…”

Section: Abstract: App Kasumi-1 Aml1/eto Panobinostatmentioning

confidence: 99%

Increased expression of amyloid precursor protein promotes proliferation and migration of AML1/ETO-positive leukemia cells and be inhibited by panobinostat

Wang¹,

Ding²,

Jiang³

et al. 2015

neo

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Amyloid precursor protein (APP) is a highly conserved integral membrane protein extensively expressed in various types of cells. Previously we found that overexpression of APP in patients with AML1/ETO-positive acute myeloid leukemia (AML) associated with a higher incidence of extramedullary infiltrationin and indicate a poor prognosis. In this study, we attempted to define the roles of APP in AML1/ETO-positive leukemia cells. Western blotting and qRT-PCR analysis showed that protein levels of APP are significantly higher in Kasumi-1, a t(8;21)/ AML1/ETO-positive M2-type AML cell line. Stable knockdown of APP by lentivirus-based RNA interference (RNAi) dramatically impaired colony-formation and migration ability of Kasumi-1 cells, whereas APP knockdown had very little effect on cell viability, apoptosis, cell cycle and differentiation. We further explored whether the pan-histone deacetylase inhibitor panobinostat could deplete the protein levels of APP in Kasumi-1 cells. Treatment with panobinostat caused depletion of APP in Kasumi-1 cells. These findings indicate that overexpression of APP is involved in promoting proliferation and migration of AML1/ETO-positive leukemia cells and can be inhibited by panobinostat, which provide an attractive prospect for treatment of AML1/ETO-positive AML. Key words: APP, Kasumi-1, AML1/ETO, panobinostatAcute myeloid leukemia (AML) with t(8;21)(q22;q22) is a specific subtype, and is frequently associated with M2 subtype according to the French-American-British (FAB) classification. The t(8;21)(q22;q22) involves the AML1 gene on chromosome 21 and the ETO gene on chromosome 8 generating the AML1/ETO fusion gene. AML with AML1/ ETO-positive is generally considered as a favorable prognosis particularly with high-dose cytosine arabinoside (Ara-C) consolidation chemotherapy. However, the treatment outcomes are not satisfactory for a high relapse rate within one year about 30% or more[1-2]. As for the assessment of prognosis of AML patients with AML1/ETO-positive, many other elements including additional chromosomal aberrations, individual genes mutations, and clinical course should be considered.Amyloid precursor protein (APP) is a highly evolutionary conserved protein. The gene for human APP is on chromosome 21q21.3 and encode a type I integral membrane protein.APP can participate in transmembrane signaling events due to its highly conserved extracellular and intracellular domains, which plays important roles in many physiological processes [3][4][5][6][7]. Many recent studies have indicated that APP is overexpressed commonly in solid tumors and mainly involved in promoting proliferation of tumor cells, including oral squamous cell carcinoma [8], pancreatic cancer cells [9], parathyroid tumor [10], and breast cancer [11]. APP was also found significantly higher in AML with abnormal chromosome 21 compared to a control group of AML with normal cytogenetics using oligonucleotide arrays [12]. Our previous study found that overexpression of APP in patients with AML1/ETO-positive AML has ...

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Trans‐synaptic mechanisms orchestrated by mammalian synaptic cell adhesion molecules

Kim

Wulschner

et al. 2022

BioEssays

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Bidirectional trans‐synaptic signaling is essential for the formation, maturation, and plasticity of synaptic connections. Synaptic cell adhesion molecules (CAMs) are prime drivers in shaping the identities of trans‐synaptic signaling pathways. A series of recent studies provide evidence that diverse presynaptic cell adhesion proteins dictate the regulation of specific synaptic properties in postsynaptic neurons. Focusing on mammalian synaptic CAMs, this article outlines several exemplary cases supporting this notion and highlights how these trans‐synaptic signaling pathways collectively contribute to the specificity and diversity of neural circuit architecture.

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Presynaptic and Postsynaptic Interaction of the Amyloid Precursor Protein Promotes Peripheral and Central Synaptogenesis

Cited by 211 publications

References 48 publications

Genetic Suppression of Transgenic APP Rescues Hypersynchronous Network Activity in a Mouse Model of Alzeimer's Disease

Genetic Suppression of Transgenic APP Rescues Hypersynchronous Network Activity in a Mouse Model of Alzeimer's Disease

Increased expression of amyloid precursor protein promotes proliferation and migration of AML1/ETO-positive leukemia cells and be inhibited by panobinostat

Trans‐synaptic mechanisms orchestrated by mammalian synaptic cell adhesion molecules

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