The role of Plasma Membrane Calcium ATPases (PMCAs) in neurodegenerative disorders

Hajieva, Parvana; Baeken, Marius W.; Moosmann, Bernd

doi:10.1016/j.neulet.2017.09.033

Cited by 22 publications

(14 citation statements)

References 144 publications

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“…As introduced earlier, we discovered and validated the PMCA as a Cindr binding partner (Table S1; Figure 1E), consistent with a potential role in calcium homeostasis. PMCA removes cytoplasmic Ca 2+ , thereby maintaining appropriate concentrations for cell signaling and neurotransmission (Hajieva et al, 2018). Loss of cindr resulted in a 2-fold increase of PMCA expression at the NMJ (Figures 4C and 4D).…”

Section: Resultsmentioning

confidence: 99%

“…Altered Ca 2+ handling has also been linked to AD pathogenesis (Frere and Slutsky, 2018), in which PMCA has been implicated (Berrocal et al, 2012; Mata et al, 2011). PMCA is a Ca 2+ efflux pump with an established requirement for neuronal Ca 2+ homeostasis (Hajieva et al, 2018). We were able to rescue cindr phenotypes either directly through increasing extracellular [Ca 2+ ] or indirectly by manipulating buffer pH to suppress PMCA activity; however, we cannot exclude the possibility that other Ca 2+ channels or transporters may participate.…”

Section: Discussionmentioning

confidence: 99%

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cindr, the Drosophila Homolog of the CD2AP Alzheimer’s Disease Risk Gene, Is Required for Synaptic Transmission and Proteostasis

et al. 2019

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

cindr, the Drosophila Homolog of the CD2AP Alzheimer’s Disease Risk Gene, Is Required for Synaptic Transmission and Proteostasis

et al. 2019

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“…Rat cortical astrocytes AD, PD, cerebellar ataxias, sensory neuron diseases Stauffer et al, 1995;Fresu et al, 1999;Kurnellas et al, 2007;Empson et al, 2010;Hajieva et al, 2018;Strehler and Thayer, 2018 PMCA3 -Cerebellum, cerebral cortex (Human) -Cerebellum and hippocampus (Rat)…”

Section: Pathophysiological Role Of Plasma Membrane Calcium Atpasesmentioning

confidence: 99%

The Role of TRP Channels and PMCA in Brain Disorders: Intracellular Calcium and pH Homeostasis

Hwang

Lee

Kim

2021

Front. Cell Dev. Biol.

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Brain disorders include neurodegenerative diseases (NDs) with different conditions that primarily affect the neurons and glia in the brain. However, the risk factors and pathophysiological mechanisms of NDs have not been fully elucidated. Homeostasis of intracellular Ca2+ concentration and intracellular pH (pHi) is crucial for cell function. The regulatory processes of these ionic mechanisms may be absent or excessive in pathological conditions, leading to a loss of cell death in distinct regions of ND patients. Herein, we review the potential involvement of transient receptor potential (TRP) channels in NDs, where disrupted Ca2+ homeostasis leads to cell death. The capability of TRP channels to restore or excite the cell through Ca2+ regulation depending on the level of plasma membrane Ca2+ ATPase (PMCA) activity is discussed in detail. As PMCA simultaneously affects intracellular Ca2+ regulation as well as pHi, TRP channels and PMCA thus play vital roles in modulating ionic homeostasis in various cell types or specific regions of the brain where the TRP channels and PMCA are expressed. For this reason, the dysfunction of TRP channels and/or PMCA under pathological conditions disrupts neuronal homeostasis due to abnormal Ca2+ and pH levels in the brain, resulting in various NDs. This review addresses the function of TRP channels and PMCA in controlling intracellular Ca2+ and pH, which may provide novel targets for treating NDs.

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“…1. Many studies have shown that Aβ aggregates and tau induce significant increases in cytosolic [Ca 2+ ]; several mechanisms have been reported for this effect, from the inhibition of Ca 2+ extrusion through the plasma membrane Ca 2+ ATPase or the Na/Ca 2+ exchanger, to the activation of Ca 2+ entry through voltage-or receptor-operated Ca 2+ channels, and including the possible direct interaction of the Aβ oligomers with the lipid bilayer to form pores [29][30][31][32][33][34][35].…”

Section: Dysregulation Of Ca 2+ Signaling In Aging and Neurodegenerationmentioning

confidence: 99%

The Role of Ca2+ Signaling in Aging and Neurodegeneration: Insights from Caenorhabditis elegans Models

Álvarez

Alvarez-Illera

García-Casas

et al. 2020

Cells

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Ca2+ is a ubiquitous second messenger that plays an essential role in physiological processes such as muscle contraction, neuronal secretion, and cell proliferation or differentiation. There is ample evidence that the dysregulation of Ca2+ signaling is one of the key events in the development of neurodegenerative processes, an idea called the “calcium hypothesis” of neurodegeneration. Caenorhabditis elegans (C. elegans) is a very good model for the study of aging and neurodegeneration. In fact, many of the signaling pathways involved in longevity were first discovered in this nematode, and many models of neurodegenerative diseases have also been developed therein, either through mutations in the worm genome or by expressing human proteins involved in neurodegeneration (β-amyloid, α-synuclein, polyglutamine, or others) in defined worm tissues. The worm is completely transparent throughout its whole life, which makes it possible to carry out Ca2+ dynamics studies in vivo at any time, by expressing Ca2+ fluorescent probes in defined worm tissues, and even in specific organelles such as mitochondria. This review will summarize the evidence obtained using this model organism to understand the role of Ca2+ signaling in aging and neurodegeneration.

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The role of Plasma Membrane Calcium ATPases (PMCAs) in neurodegenerative disorders

Cited by 22 publications

References 144 publications

cindr, the Drosophila Homolog of the CD2AP Alzheimer’s Disease Risk Gene, Is Required for Synaptic Transmission and Proteostasis

cindr, the Drosophila Homolog of the CD2AP Alzheimer’s Disease Risk Gene, Is Required for Synaptic Transmission and Proteostasis

The Role of TRP Channels and PMCA in Brain Disorders: Intracellular Calcium and pH Homeostasis

The Role of Ca2+ Signaling in Aging and Neurodegeneration: Insights from Caenorhabditis elegans Models

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