A splice site mutation in ATP6AP2 causes X-linked intellectual disability, epilepsy, and parkinsonism

Gupta, Harish; Vengoechea, Jaime; Sahaya, Kinshuk; Virmani, Tuhin

doi:10.1016/j.parkreldis.2015.10.001

Cited by 35 publications

(33 citation statements)

References 4 publications

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“…In another family, 2 affected siblings suffering from either XLID or parkinsonism have been described carrying a putative splice site mutation in ATP6AP2 (c.168+6T>A), downstream of exon 2. However, the functional relevance of this putative variant to splicing and ATP6AP2 function remains to be studied (16). To date, the role of ATP6AP2 in development and function of the mammalian CNS remains largely Figure 2.…”

Section: Atp6ap2 Variant Impairs Cns Development and Neuronal Survivamentioning

confidence: 99%

ATP6AP2 variant impairs CNS development and neuronal survival to cause fulminant neurodegeneration

Hirose¹,

Cabrera-Socorro²,

Chitayat³

et al. 2019

Journal of Clinical Investigation

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Section: Atp6ap2 Variant Impairs Cns Development and Neuronal Survivamentioning

confidence: 99%

ATP6AP2 variant impairs CNS development and neuronal survival to cause fulminant neurodegeneration

Hirose¹,

Cabrera-Socorro²,

Chitayat³

et al. 2019

Journal of Clinical Investigation

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“…This is yet another constituent of V-ATPase but was also described to act as prorenin receptor and to modulate Wnt signaling (Cruciat et al, 2010). Moreover, ATP6ap2 mutations have been associated with mental disorders, brain atrophy as well as white matter thinning (Gupta, Vengoechea, Sahaya, & Virmani, 2015).…”

Section: Discussionmentioning

confidence: 99%

Rescuing the negative impact of human endogenous retrovirus envelope protein on oligodendroglial differentiation and myelination

Göttle

Förster

Gruchot

et al. 2018

Glia

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Remyelination in the adult CNS depends on activation, differentiation, and functional integration of resident oligodendroglial precursor cells (OPCs) and constitutes the only spontaneous neuroregenerative process able to compensate for functional deficits upon loss of oligodendrocytes and myelin sheaths as it is observed in multiple sclerosis. The proteins encoded by p57kip2‐ and by human endogenous retrovirus type W (pHERV‐W) envelope genes were previously identified as negative regulators of OPC maturation. We here focused on the activity of the ENV protein and investigated how it can be neutralized for an improved myelin repair. We could demonstrate that myelination in vitro is severely affected by this protein but that application of an anti‐ENV neutralizing antibody, currently investigated in clinical trials, can rescue the generation of internodes. We then compared p57kip2 and ENV dependent inhibitory mechanisms and found that a dominant negative version of the p57kip2 protein can equally save OPCs from myelination failure in response to ENV‐mediated TLR4 activation. Additional experiments addressing p57kip2's underlying mode of action revealed a direct interaction with ATP6v1d, a central component of a vascular ATPase. Its pharmacological blocking was then shown to exert an analogous myelination rescue effect in presence of the ENV protein. Therefore, our study provides mechanistic insights into oligodendroglial inhibition processes and presents three different means to counteract the anti‐myelination effect of the ENV protein. These observations are therefore of interest in light of understanding the complexity of the numerous oligodendroglial inhibitors and might promote the establishment of novel regenerative therapies.

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“…ATP6AP2 gene mutations also have been associated with Xlinked mental retardation, epilepsy, and parkinsonism, [73][74][75] but these single nucleotide polymorphisms are limited to single families of 2 to 7 affected individuals.…”

Section: Role Of the Prr In Bp Regulationmentioning

confidence: 99%

The (pro)renin receptor: an emerging player in hypertension and metabolic syndrome

Ramkumar

Kohan

2019

Kidney International

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The (pro)renin receptor (PRR) is a multifunctional protein that is expressed in multiple organs. Binding of prorenin/ renin to the PRR activates angiotensin II-dependent and angiotensin II-independent pathways. The PRR is also involved in autophagy and Wnt/ß catenin signaling, functions that are not contingent on prorenin binding. Emerging evidence suggests that the PRR plays an important role in blood pressure regulation and glucose and lipid metabolism. Herein, we review PRR function in health and disease, with particular emphasis on hypertension and the metabolic syndrome.

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A splice site mutation in ATP6AP2 causes X-linked intellectual disability, epilepsy, and parkinsonism

Cited by 35 publications

References 4 publications

ATP6AP2 variant impairs CNS development and neuronal survival to cause fulminant neurodegeneration

ATP6AP2 variant impairs CNS development and neuronal survival to cause fulminant neurodegeneration

Rescuing the negative impact of human endogenous retrovirus envelope protein on oligodendroglial differentiation and myelination

The (pro)renin receptor: an emerging player in hypertension and metabolic syndrome

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