β-catenin aggregation in models of ALS motor neurons: GSK3β inhibition effect and neuronal differentiation

Pinto, Cristina; Medinas, Danilo B.; Fuentes-Villalobos, Francisco; Maripillán, Jaime; Castro, Ariel F.; Martı́nez, Agustı́n D.; Osses, Nelson; Hetz, Claudio; Henríquez, Juan Pablo

doi:10.1016/j.nbd.2019.104497

Cited by 18 publications

(17 citation statements)

References 73 publications

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“…Expression of mutant SOD1, which is associated with familial ALS, in the NSC34 motor neuron cell line accumulates cytosolic β-catenin and impairs neuronal differentiation. Remarkably, pharmacological inhibition of the GSK3β reverts both β-catenin aggregation and mutant SOD1-induced aberrant neuronal differentiation (Pinto and others 2019).…”

Section: Wnt/β-catenin Signaling In Neural Stem Cell Homeostasismentioning

confidence: 99%

Wnt/β-Catenin Signaling in Neural Stem Cell Homeostasis and Neurological Diseases

et al. 2020

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Neural stem/progenitor cells (NSCs) maintain the ability of self-renewal and differentiation and compose the complex nervous system. Wnt signaling is thought to control the balance of NSC proliferation and differentiation via the transcriptional coactivator β-catenin during brain development and adult tissue homeostasis. Disruption of Wnt signaling may result in developmental defects and neurological diseases. Here, we summarize recent findings of the roles of Wnt/β-catenin signaling components in NSC homeostasis for the regulation of functional brain circuits. We also suggest that the potential role of Wnt/β-catenin signaling might lead to new therapeutic strategies for neurological diseases, including, but not limited to, spinal cord injury, Alzheimer’s disease, Parkinson’s disease, and depression.

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Section: Wnt/β-catenin Signaling In Neural Stem Cell Homeostasismentioning

confidence: 99%

Wnt/β-Catenin Signaling in Neural Stem Cell Homeostasis and Neurological Diseases

et al. 2020

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“…The nuclear translocation of β–catenin is an important sign of activation of the WNT/β–catenin signaling pathway. Pinto et al [ 34 ] also found markedly increased β–catenin accumulation in ALS motor neurons, including increased supramolecular structures in SOD1–G93A mice and the NSC34 motor neuron–like cell line. Thus, based on the evidence outlined above, WNT/β–catenin signaling is hyperactivated in ALS transgenic mice, but it is unclear whether this alteration is beneficial or harmful.…”

Section: Alteration Of Wnt Signaling In Alsmentioning

confidence: 99%

“…Cytosolic β–catenin proteins aggregate abnormally in the ALS in vitro model, which is constructed using motor neuron–like NSC34 cells that stably express G93A mutant SOD1 [ 34 , 50 ] ( Figure 2 Aa,Bb and Figure 3 a). Abnormal β–catenin inmutated hSOD1 NSC34 cells does not co–localize with common protein aggregates cleared by degradative pathways [ 34 ], because the abnormal β–catenin does not form insoluble protein aggregates and may assemble as a three–dimensional structure of amorphous aggregates, in which monomers are assembled randomly. Moreover, the abnormal presence of peripheral β–catenin structures is associated with impaired cell–cell interaction and decreased neuronal differentiation [ 34 ].…”

Section: Dysregulated Wnt/β–catenin Signaling In Neurons and Glial Cellsmentioning

confidence: 99%

“…It is surprising that disassembly of accumulated β–catenin structures can rescue the morphological differentiation of ALS–like motor neurons [ 34 ]. In the neuronal model of Huntington’s disease (HD) in drosophila, reduced β–catenin levels have a neuroprotective effect and extend the lifespan of HD flies [ 51 ].…”

Section: Dysregulated Wnt/β–catenin Signaling In Neurons and Glial Cellsmentioning

confidence: 99%

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Potential Roles of the WNT Signaling Pathway in Amyotrophic Lateral Sclerosis

Jiang

Guan

Zhao

et al. 2021

Cells

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The WNT signaling pathway plays an important role in the physiological and pathophysiological processes of the central nervous system and the neurodegenerative disease amyotrophic lateral sclerosis (ALS). We reviewed the literature pertinent to WNT/β–catenin signaling in ALS from cellular studies, animal models, and human clinical trials. WNT, WNT receptors, and other components of the WNT signaling pathway are expressed in both ALS patients and transgenic mice, and are involved in the pathogenesis of ALS. Studies have shown that abnormal activation of the WNT/β–catenin signaling pathway is related to neuronal degeneration and glial cell proliferation. WNT/Ca2+ signaling is associated with the pro–inflammatory phenotype of microglia; data on the muscle skeletal receptor Tyr kinase receptor in superoxide dismutase–1–G93A mice indicate that gene therapy is necessary for successful treatment of ALS. The varying profiles of lipoprotein receptor–related protein 4 antibodies in different ethnic groups suggest that individual treatment and multifactorial personalized approaches may be necessary for effective ALS therapy. In conclusion, the WNT signaling pathway is important to the ALS disease process, making it a likely therapeutic target.

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“…The role of Wnt signaling is highly debated in ALS, where the degeneration of motor neurons in the brain cortex could be partly due to the alterations of some Wnt effectors, in particular the dysregulation in β-catenin homeostasis [ 78 , 79 ].…”

Section: Channels-wnt-dependent Signaling Axes In Diseasesmentioning

confidence: 99%

From Channels to Canonical Wnt Signaling: A Pathological Perspective

Muccioli

Brillo

Chieregato

et al. 2021

IJMS

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Wnt signaling is an important pathway mainly active during embryonic development and controlling cell proliferation. This regulatory pathway is aberrantly activated in several human diseases. Ion channels are known modulators of several important cellular functions ranging from the tuning of the membrane potential to modulation of intracellular pathways, in particular the influence of ion channels in Wnt signaling regulation has been widely investigated. This review will discuss the known links between ion channels and canonical Wnt signaling, focusing on their possible roles in human metabolic diseases, neurological disorders, and cancer.

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β-catenin aggregation in models of ALS motor neurons: GSK3β inhibition effect and neuronal differentiation

Cited by 18 publications

References 73 publications

Wnt/β-Catenin Signaling in Neural Stem Cell Homeostasis and Neurological Diseases

Wnt/β-Catenin Signaling in Neural Stem Cell Homeostasis and Neurological Diseases

Potential Roles of the WNT Signaling Pathway in Amyotrophic Lateral Sclerosis

From Channels to Canonical Wnt Signaling: A Pathological Perspective

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