Progenitor cells from the adult mouse brain acquire a neuronal phenotype in response to β-amyloid

Calafiore, Marco; Battaglia, Giuseppe; Zappalà, Agata; Trovato-Salinaro, Elisa; Caraci, Filippo; Caruso, Massimo; Vancheri, Carlo; Sortino, Maria Angela; Nicoletti, Ferdinando; Copani, Agata

doi:10.1016/j.neurobiolaging.2005.03.019

Cited by 28 publications

(30 citation statements)

References 30 publications

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“…The fetal brain has been reported to display a number of biochemical similarities to the AD brain, namely the presence of A␤ and A␤PP (46, 47), hyperphosphorylated tau (48), and presenilin-1 expression (49). That amyloidogenic pathways are involved in neurogenesis has been reported recently by a number of workers (5,6,37,38). In this context, an increase in neurogenesis has been reported in young transgenic mice overexpressing human mutant APP (7,8).…”

Section: Discussionmentioning

confidence: 97%

Differential Processing of Amyloid-β Precursor Protein Directs Human Embryonic Stem Cell Proliferation and Differentiation into Neuronal Precursor Cells

Porayette

Gallego

Kaltcheva

et al. 2009

Journal of Biological Chemistry

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The amyloid-␤ precursor protein (A␤PP) is a ubiquitously expressed transmembrane protein whose cleavage product, the amyloid-␤ (A␤) protein, is deposited in amyloid plaques in neurodegenerative conditions such as Alzheimer disease, Down syndrome, and head injury. We recently reported that this protein, normally associated with neurodegenerative conditions, is expressed by human embryonic stem cells (hESCs). We now report that the differential processing of A␤PP via secretase enzymes regulates the proliferation and differentiation of hESCs. hESCs endogenously produce amyloid-␤, which when added exogenously in soluble and fibrillar forms but not oligomeric forms markedly increased hESC proliferation. The inhibition of A␤PP cleavage by ␤-secretase inhibitors significantly suppressed hESC proliferation and promoted nestin expression, an early marker of neural precursor cell (NPC) formation. The induction of NPC differentiation via the non-amyloidogenic pathway was confirmed by the addition of secreted A␤PP␣, which suppressed hESC proliferation and promoted the formation of NPCs. Together these data suggest that differential processing of A␤PP is normally required for embryonic neurogenesis.The amyloid-␤ precursor protein (A␤PP) 5 is a ubiquitously expressed transmembrane protein whose cleavage product, the amyloid-␤ (A␤) protein, is deposited in amyloid plaques in the aged brain, following head injury, and in the neurodegenerative conditions of Alzheimer disease (AD) and Down syndrome (DS). A␤PP has structural similarity to growth factors (1) and modulates several important neurotrophic functions, including neuritogenesis, synaptogenesis, and synaptic plasticity (2). The function of A␤PP during early embryogenesis and neurogenesis has not been well described.A␤PP is processed by at least two pathways, the non-amyloidogenic and amyloidogenic pathways. Non-amyloidogenic processing of A␤PP yields secreted A␤PP␣ (sA␤PP␣), the secreted extracellular domain of A␤PP that acts as a growth factor for many cell types and promotes neuritogenesis (3). Amyloidogenic processing of A␤PP releases sA␤PP␤, the A␤PP intracellular domain, and A␤ proteins. The A␤ protein has both neurotoxic and neurotrophic properties (4) dependent on the differentiation state of the neuron; A␤ is neurotoxic to differentiating neurons via a mechanism involving differentiation-associated increases in the phosphorylation of the microtubule-associated protein tau (5) but neurotrophic to undifferentiated embryonic neurons. Evidence supporting a neurotrophic function for A␤ during development include its neurogenic activity toward rat neural stem cells (4 -6). Consistent with these data, two studies have demonstrated increased hippocampal neurogenesis in young transgenic mice overexpressing human APP Sw,Ind (7,8).Recently we reported that human embryonic stem cells (hESCs) express A␤PP and that both the stemness of the cells and the pregnancy-associated hormone human chorionic gonadotropin alter A␤PP expression (9). These results suggest a functional role fo...

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Section: Discussionmentioning

confidence: 97%

Differential Processing of Amyloid-β Precursor Protein Directs Human Embryonic Stem Cell Proliferation and Differentiation into Neuronal Precursor Cells

Porayette

Gallego

Kaltcheva

et al. 2009

Journal of Biological Chemistry

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“…Conversely, A␤ promotes the neuronal differentiation of cultured neural stem cells from the newborn mouse hippocampus or adult mouse subventricular zone (13,14). This inconsistency may not result from differences of the state of aggregation (fibril of pre-fibril) or the concentration of A␤ used in these experiments.…”

Section: Discussionmentioning

confidence: 98%

“…However, contradictory findings have been reported regarding whether hippocampal neurogenesis in AD mouse models is impaired or enhanced; most AD mouse models (PrP-APP SW Tg, PDGF-APP V717F Tg, PS1 P117L Tg, PS1 M146V knockin) show impaired hippocampal neurogenesis (6 -11), but in one AD mouse model (PDGF-APP SW, In Tg), increased neurogenesis was reported (12). The in vitro effects of A␤ peptide on the proliferation and differentiation of neural stem/progenitor cells are also controversial (9,(13)(14)(15). Thus, the question of whether the brain microenvironment is altered by A␤, rendering it toxic to progenitor cells and immature neurons, still remains unanswered.…”

mentioning

confidence: 99%

Differential Regulation of Basic Helix-Loop-Helix Factors Mash1 and Olig2 by β-Amyloid Accelerates Both Differentiation and Death of Cultured Neural Stem/Progenitor Cells

Uchida

Nakano

Gomi

et al. 2007

Journal of Biological Chemistry

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“…Neurogenesis is induced by A ␤ 42 but not by A ␤ 40 and the neurogenic eff ect of A ␤ is not dependent on soluble factors released from the NSC progeny. Th ese results suggest that A ␤ may have positive as well as deleterious actions, and that knowledge of the mechanisms involved in the former could be valuable in preventing and treating AD [100][101][102] . If a general feature of AD is the loss of proliferation of NSCs, then loss of proliferation in the SGZ of the hippocampus may contribute to the observed loss of memory in AD.…”

Section: Ad and Neural Stem Cellsmentioning

confidence: 94%

Nerve Growth Factor, Neural Stem Cells and Alzheimer’s Disease

2006

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The protein family of the neurotrophins (NTs) comprises structurally and functionally related molecules such as nerve growth factor (NGF) which influences the proliferation, differentiation, survival and death of neuronal cells. In addition to their established functions for cell survival, NTs also mediate higher brain activities such as learning and memory. Changes in NT expression levels have thus been implicated in neurological diseases such as Alzheimer’s disease (AD), an age-related neurodegenerative disorder that is characterized by progressive loss of memory and deterioration of higher cognitive functions. The present review provides an overview of the functional role of NGF in neural stem cells and AD while pointing to a potential application of this peptide for the treatment of AD.

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Progenitor cells from the adult mouse brain acquire a neuronal phenotype in response to β-amyloid

Cited by 28 publications

References 30 publications

Differential Processing of Amyloid-β Precursor Protein Directs Human Embryonic Stem Cell Proliferation and Differentiation into Neuronal Precursor Cells

Differential Processing of Amyloid-β Precursor Protein Directs Human Embryonic Stem Cell Proliferation and Differentiation into Neuronal Precursor Cells

Differential Regulation of Basic Helix-Loop-Helix Factors Mash1 and Olig2 by β-Amyloid Accelerates Both Differentiation and Death of Cultured Neural Stem/Progenitor Cells

Nerve Growth Factor, Neural Stem Cells and Alzheimer’s Disease

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