Cellular Functions of the Amyloid Precursor Protein from Development to Dementia

Kant, Rik van der; Goldstein, Lawrence S.B.

doi:10.1016/j.devcel.2015.01.022

Cited by 203 publications

(145 citation statements)

References 156 publications

(162 reference statements)

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“…Thus, having normal levels of thyroid hormone help maintain APP levels to a minimum and subsequently preventing Aβ overproduction. Surprisingly, two independent studies showed an association between the presence of the apo E4 allele and low thyroid hormone levels [40,41] suggesting that T3 also plays a critical role controlling the removal of Aβ. Interestingly, T3 appears to regulate the splicing and maturation of the tau mRNA, as previously shown [42,43] and herein.…”

Section: Discussionmentioning

confidence: 99%

Thyroid Hormone Enhances Neurite Outgrowth in Neuroscreen 1 Cells

et al. 2018

Int J Biomed Investig

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Section: Discussionmentioning

confidence: 99%

Thyroid Hormone Enhances Neurite Outgrowth in Neuroscreen 1 Cells

et al. 2018

Int J Biomed Investig

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“…The type-I transmembrane glycoprotein APP is one of the most abundant proteins in the human CNS and is ubiquitously expressed in the plasma membrane and in several organelles, such as the ER, Golgi apparatus, and mitochondria (van der Kant and Goldstein, 2015). …”

Section: Amylin Amyloids: a Comparison With The Formation And Patholomentioning

confidence: 99%

“…As extensively reviewed elsewhere (Hardy and Selkoe, 2002; Karran et al, 2011; van der Kant and Goldstein, 2015), they interact with neuronal and glial cells to cause mitochondrial dysfunction and oxidative stress, impairments of intracellular signaling pathways and synaptic plasticity, and eventually neuronal apoptosis. It is believed that these mechanisms can give rise to a positive feedback loop that facilitates the production of Aβ peptides through stimulation of the amyloidogenic pathway (Hardy and Selkoe, 2002; Karran et al, 2011; van der Kant and Goldstein, 2015). Hence, the amyloidogenic pathway seems to be more active under pathological conditions, whereas APP is preferentially processed via the secretory pathway under physiological conditions.…”

Section: Amylin Amyloids: a Comparison With The Formation And Patholomentioning

confidence: 99%

Amylin at the interface between metabolic and neurodegenerative disorders

Lutz

Meyer

2015

Front. Neurosci.

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The pancreatic peptide amylin is best known for its role as a satiation hormone in the control of food intake and as the major component of islet amyloid deposits in the pancreatic islets of patients with type 2 diabetes mellitus (T2DM). Epidemiological studies have established a clear association between metabolic and neurodegenerative disorders in general, and between T2DM and Alzheimer's disease (AD) in particular. Here, we discuss that amylin may be an important player acting at the interface between these metabolic and neurodegenerative disorders. Abnormal amylin production is a hallmark peripheral pathology both in the early (pre-diabetic) and late phases of T2DM, where hyperamylinemic (early phase) and hypoamylinemic (late phase) conditions coincide with hyper- and hypo-insulinemia, respectively. Moreover, there are notable biochemical similarities between amylin and β-amyloids (Aβ), which are both prone to amyloid plaque formation and to cytotoxic effects. Amylin's propensity to form amyloid plaques is not restricted to pancreatic islet cells, but readily extends to the CNS, where it has been found to co-localize with Aβ plaques in at least a subset of AD patients. Hence, amylin may constitute a “second amyloid” in neurodegenerative disorders such as AD. We further argue that hyperamylinemic conditions may be more relevant for the early processes of amyloid formation in the CNS, whereas hypoamylinemic conditions may be more strongly associated with late stages of central amyloid pathologies. Advancing our understanding of these temporal relationships may help to establish amylin-based interventions in the treatment of AD and other neurodegenerative disorders with metabolic comorbidities.

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“…These relatively subtle but significant phenotypes in conventional and App mutants could indicate that other APP family members may compensate for the loss of APP. Previous studies in mice suggest functional redundancy between APP and APP-like protein 2 (APLP2): APLP2 can take over APP functions in vivo (van der Kant and Goldstein, 2015). Indeed, APLP2 was found in the 29 proteins from the bEND3 derived-CM fraction (Fig.…”

Section: App Deficiency Does Not Detectably Influence Svz Architecturmentioning

confidence: 99%

Soluble APP functions as a vascular niche signal that controls adult neural stem cell number

Sato

Uchida

et al. 2017

Development

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The molecular mechanism by which NSC number is controlled in the neurogenic regions of the adult brain is not fully understood but it has been shown that vascular niche signals regulate neural stem cell (NSC) quiescence and growth. Here, we have uncovered a role for soluble amyloid precursor protein (sAPP) as a vascular niche signal in the subventricular zone (SVZ) of the lateral ventricle of the adult mouse brain. sAPP suppresses NSC growth in culture. Further in vivo studies on the role of APP in regulating NSC number in the SVZ clearly demonstrate that endothelial deletion of App causes a significant increase in the number of BrdU label-retaining NSCs in the SVZ, whereas NSC/astrocyte deletion of App has no detectable effect on the NSC number. Taken together, these results suggest that endothelial APP functions as a vascular niche signal that negatively regulates NSC growth to control the NSC number in the SVZ.

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Cellular Functions of the Amyloid Precursor Protein from Development to Dementia

Cited by 203 publications

References 156 publications

Thyroid Hormone Enhances Neurite Outgrowth in Neuroscreen 1 Cells

Thyroid Hormone Enhances Neurite Outgrowth in Neuroscreen 1 Cells

Amylin at the interface between metabolic and neurodegenerative disorders

Soluble APP functions as a vascular niche signal that controls adult neural stem cell number

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