Memory and cerebrovascular deficits recovered following angiotensin IV intervention in a mouse model of Alzheimer's disease

Royea, Jessika; Martinot, Pauline; Hamel, Edith

doi:10.1016/j.nbd.2019.104644

Cited by 34 publications

(38 citation statements)

References 51 publications

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“…IRAP therefore presents as a promising target for neurodegenerative diseases such as Alzheimer’s Disease (AD), in which there is progressive cognitive decline and memory loss. This was validated in a recent study by Royea et al (2019) in which 4 weeks of centrally administered Ang IV (1.3 nmol/day) restored short-term memory, spatial learning and spatial memory in a transgenic mouse model of AD with alternatively spliced amyloid precursor protein.…”

Section: Targeting the C-terminal Domain Of Irapmentioning

confidence: 52%

“…Evidence of changes in the brain with IRAP inhibitor treatment include normalization of hippocampal subgranular zone cellular proliferation, enhanced dendritic branching, and reduced oxidative stress ( Royea et al, 2019 ). Furthermore, treatment of primary rat hippocampal cultures with a number of different classes of IRAP inhibitors has been shown to significantly alter dendritic spine morphology and increase spine density ( Diwakarla et al, 2016a , b ; Seyer et al, 2019 ).…”

Section: Targeting the C-terminal Domain Of Irapmentioning

confidence: 99%

“…These unexpected observations were thought to potentially be due to altered brain development of the knockout mice, given there is high IRAP expression in the highly neurogenic ventricular and subventricular zone of the embryonic mouse brain, possibly implicating IRAP as having a role in neuronal development. Regardless of this finding, there is comprehensive evidence supporting the cognitive enhancing effect of IRAP inhibition ( Albiston et al, 2004 ; Lee et al, 2004 ; De Bundel et al, 2009 ; Fidalgo et al, 2019 ; Royea et al, 2019 ).…”

Section: Targeting the C-terminal Domain Of Irapmentioning

confidence: 99%

“…Much of the earlier work on elucidating the enzymatic role of IRAP have involved the use of angiotensin IV (Ang IV), a peptide inhibitor. Treatment with Ang IV or other IRAP inhibitors elicited effects on facilitation of memory ( Braszko et al, 1988 ; Wright et al, 1993 ; Albiston et al, 2008 ; De Bundel et al, 2009 ; Royea et al, 2019 ) and protection against ischemic damage ( Coleman et al, 1998 ; Faure et al, 2006a ; Park et al, 2016 ). It can be reasonably asserted that these peptide inhibitors bind to IRAP at the cell surface, as like many M1 aminopeptidases, IRAP is an integral membrane protein with its catalytic domain on the cell exterior.…”

Section: Introductionmentioning

confidence: 99%

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Is There an Interplay Between the Functional Domains of IRAP?

Vear

Gaspari

Thompson

et al. 2020

Front. Cell Dev. Biol.

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As a member of the M1 family of aminopeptidases, insulin regulated aminopeptidase (IRAP) is characterized by distinct binding motifs at the active site in the C-terminal domain that mediate the catalysis of peptide substrates. However, what makes IRAP unique in this family of enzymes is that it also possesses trafficking motifs at the N-terminal domain which regulate the movement of IRAP within different intracellular compartments. Research on the role of IRAP has focused predominantly on the C-terminus catalytic domain in different physiological and pathophysiological states ranging from pregnancy to memory loss. Many of these studies have utilized IRAP inhibitors, that bind competitively to the active site of IRAP, to explore the functional significance of its catalytic activity. However, it is unknown whether these inhibitors are able to access intracellular sites where IRAP is predominantly located in a basal state as the enzyme may need to be at the cell surface for the inhibitors to mediate their effects. This property of IRAP has often been overlooked. Interestingly, in some pathophysiological states, the distribution of IRAP is altered. This, together with the fact that IRAP possesses trafficking motifs, suggest the localization of IRAP may play an important role in defining its physiological or pathological functions and provide insights into the interplay between the two functional domains of the protein.

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Section: Targeting the C-terminal Domain Of Irapmentioning

confidence: 52%

Section: Targeting the C-terminal Domain Of Irapmentioning

confidence: 99%

Section: Targeting the C-terminal Domain Of Irapmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Is There an Interplay Between the Functional Domains of IRAP?

Vear

Gaspari

Thompson

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…AD is an age-related, progressive, irreversible neurodegenerative disease that leads to the loss of selected neurons in the basal forebrain, almond nucleus, hippocampus and cortex, as well as the progressive deceleration of cognition and memory [1][2][3][4]. It is characterized by an insidious development of hippocampal pathology [5,6]. The changes in neurogenesis observed during the initial stages and progression of AD demonstrated that modulation of the new productions of neurons at neurogenic sites may exert profound effects on hippocampal function [1].…”

Section: Introductionmentioning

confidence: 99%

BMP4 overexpression induces upregulation of APP/TAU and memory deficits in Alzheimer’s disease

Zhang

et al. 2020

Preprint

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Background: Alzheimer's disease (AD) is a chronic progressive degenerative disease of the nervous system. Its pathogenesis is complex, which is related to abnormal expression of the amyloid b-protein (Ab), APP, and TAU protein. Evidence has demonstrated that bone morphogenetic protein 4 (BMP4) is highly expressed in transgenic mouse models of AD, and endogenous level of BMP4 mainly affects hippocampal function.Methods: To determine whether BMP4 participates in AD development, transgenic mice were constructed with overexpression of BMP4 under control of the neuron-specific enolase (NSE) promoter. We also performed MTT, FACS, Transfection, TUNEL and Western blotting assay to define the role of BMP4 in cells.Results: We found that middle-aged BMP4 transgenic mice exhibited memory disorder via Morris water maze experiment. Moreover, the hippocampal tissues have high expression of AD related proteins including APP, Ab, PSEN-1, TAU, P-TAU (Thr181), and P-TAU (Thr231) proteins. Furthermore, in multiple cell lines, overexpression of BMP4 increased the expression of AD related proteins, whereas downregulation of BMP4 demonstrated opposed effects. Consistently, BMP4 modulation participated in cell apoptosis via regulation of BAX and Bcl-2 expression in cells. Conclusion: Our findings indicate that BMP4 overexpression might be a potential factor to induce AD.

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Brain angiotensin II and angiotensin IV receptors as potential Alzheimer’s disease therapeutic targets

Royea

Hamel

2020

GeroScience

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Memory and cerebrovascular deficits recovered following angiotensin IV intervention in a mouse model of Alzheimer's disease

Cited by 34 publications

References 51 publications

Is There an Interplay Between the Functional Domains of IRAP?

Is There an Interplay Between the Functional Domains of IRAP?

BMP4 overexpression induces upregulation of APP/TAU and memory deficits in Alzheimer’s disease

Brain angiotensin II and angiotensin IV receptors as potential Alzheimer’s disease therapeutic targets

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