Role of Wnt1 and Fzd1 in the spinal cord pathogenesis of amyotrophic lateral sclerosis-transgenic mice

Wang, Shanshan; Guan, Yingjun; Chen, Yanchun; Li, Xiaojin; Zhang, Caixia; Yu, Li; Zhou, Fenghua; Wang, Xin

doi:10.1007/s10529-013-1199-1

Cited by 32 publications

(37 citation statements)

References 15 publications

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“…Several studies have shown that this pathway is upregulated in motor neurons of ASL model mice [32][33][34][35]. In the spinal cord of SOD1(G93A) ALS transgenic mice, expression of Wnt2, Wnt7a and GSK-3beta has been determined [32].…”

Section: Als and Wnt/beta-catenin Pathwaymentioning

confidence: 99%

“…Changes in Wnt5a and Fzd2 expression in the spinal cord of SOD1(G93A) transgenic mice (ALS), SOD1(G93A) transfected NSC-34 cells and primary cultures of astrocytes from SOD1(G93A) transgenic mice have been observed [35]. Expression of Wnt1 and Fzd1 has been found to be increased in the spinal cords of SOD1G93A ALS transgenic mice [34]. In the in vitro model of ALS (G93A mutated forms of human Cu/Zn superoxide dismutase-1; SOD1), a cytosolic aggregation of beta-catenin has been observed.…”

Section: Als and Wnt/beta-catenin Pathwaymentioning

confidence: 99%

“…Moreover, riluzole enhances Wnt/beta-catenin signaling in the primary screen both in HT22 neuronal cells and in adult hippocampal progenitor cells [40]. As the Wnt/beta-catenin pathway is upregulated, at least in genetic ALS mice [32][33][34][35], this can partly explain poor results in trials testing riluzole in ALS as shown previously [12][13][14][15]. Lithium, an activator of the Wnt/beta catenin signaling, has also been evaluated as a treatment for ALS [41].…”

Section: Als and Riluzolementioning

confidence: 99%

“…In the genetic ALS G93A mouse model, there is a marked neuroprotection induced by lithium, which delayed disease onset and duration and augmented the life span. The use of the enhancer Wnt/beta-catenin lithium can be discussed in ALS in which the Wnt/beta-catenin pathway has been shown to be upregulated in several animal studies [32][33][34][35]. GSK-3beta-inhibitor lithium chloride enhances activation of the canonical Wnt signaling [42][43][44].…”

Section: Als and Riluzolementioning

confidence: 99%

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Amyotrophic Lateral Sclerosis: Role of the Canonical Wnt/Beta- Catenin Pathway and PPAR Gamma

Lecarpentier¹,

Vallée²

2016

Update on Amyotrophic Lateral Sclerosis

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Amyotrophic lateral sclerosis (ALS) is one of the most common adult-onset debilitating neurodegenerative diseases (NDs) which is characterized by a chronic progressive degeneration of upper and lower motor neurons, resulting in muscular atrophy, paralysis and ultimately death. It has been established that in ALS, the canonical Wnt/ beta-catenin pathway is upregulated. Peroxisome proliferator-activated receptor gamma (PPAR gamma) generally varies in opposite way compared with the Wnt/betacatenin signaling. Several studies carried out on ALS transgenic mice have shown the beneficial effects induced after treatment by PPAR agonists partly due to antiinflammatory effects induced by PPAR gamma. The coupling between the Wnt/betacatenin signaling and PPAR gamma has led to divide NDs into two classes: NDs in which the Wnt/beta-catenin pathway is upregulated whereas PPAR gamma is downregulated (ALS, Parkinson's disease, Huntington's disease and Friedreich's ataxia); and NDs in which the Wnt-beta-catenin pathway is downregulated while PPAR gamma is upregulated (Alzheimer's disease, bipolar disorder and schizophrenia).

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Section: Als and Wnt/beta-catenin Pathwaymentioning

confidence: 99%

Section: Als and Wnt/beta-catenin Pathwaymentioning

confidence: 99%

Section: Als and Riluzolementioning

confidence: 99%

Section: Als and Riluzolementioning

confidence: 99%

See 2 more Smart Citations

Amyotrophic Lateral Sclerosis: Role of the Canonical Wnt/Beta- Catenin Pathway and PPAR Gamma

Lecarpentier¹,

Vallée²

2016

Update on Amyotrophic Lateral Sclerosis

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“…A growing body of evidence suggests that Wnt signaling may be involved in homeostasis and disease progression in adult tissues, [17][18][19][20][21][22][23][24][25][26] including the spinal cord.…”

mentioning

confidence: 99%

Wnts Are Expressed in the Spinal Cord of Adult Mice and Are Differentially Induced after Injury

González-Fernández

Fernández-Martos

Shields

et al. 2014

Journal of Neurotrauma

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The Wnt family of proteins plays key roles during central nervous system development and has been involved in several neuropathologies during adulthood, including spinal cord injury (SCI). However, Wnts expression knowledge is relatively limited during adult stages. Here, we sought to define the Wnt family expression pattern after SCI in adult mice by using quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Under physiological conditions, the messenger RNAs (mRNAs) of most Wnt ligands, inhibitors, receptors, and coreceptors are constitutively expressed in healthy adult mice. After dorsal hemisection, we found significant time-dependent variations, with a prominent upregulation of Wnt inhibitory factor 1 (Wif1). IHC against Frizzled (Fz) 1 and Fz4, as representatives of late and acute upregulated receptors, showed a differential expression in the uninjured spinal cord of Fz1 by neurons and oligodendrocytes and Fz4 by astrocytes. After injury, both receptors were maintained in the same type of cells. Finally, by using BATgal reporter mice, our results revealed active b-catenin signaling in neurons of the dorsal horn and cells of the central canal of uninjured spinal cords, besides a lack of additional SCI-induced activation.In conclusion, we demonstrate Wnt expression in the adult spinal cord of mice that is modulated by SCI, which differs from that previously described in rats. Further, Fz receptors are differentially expressed by neurons and glial cells, suggestive for cell-specific patterns and thus diverse physiological roles. Further studies will help toward in-depth characterization of the role of all Wnt factors and receptors described and eventually allow for the design of novel therapies.

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Altered expression of atypical PKC and Ryk in the spinal cord of a mouse model of amyotrophic lateral sclerosis

Tury

Tolentino

Zou

2014

Developmental Neurobiology

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive paralysis due to the selective death of motor neurons of unknown causes. Increasing evidence indicates that Wnt signaling is altered in ALS. In this study, we focused on two non-canonical Wnt signaling components, atypical PKC (aPKC) and a Wnt receptor, Ryk, in a mouse model of ALS, SOD1 (G93A). aPKC mediates Wnt signaling to regulate growth cone guidance, axon differentiation and cell survival. Ryk is a Wnt repulsive receptor that regulates axon guidance and inhibits regeneration after spinal cord injury. aPKC expression was increased in motor neurons of the lumbar spinal cord in SOD1 (G93A) mice at different stages. Interestingly, aPKC was colocalized with SOD1 in motor neuron cell bodies and extracellular aggregates, and aPKC-containing extracellular aggregates increased with disease progression. Biochemical fractionation showed that aPKC protein level was increased in the detergent-insoluble protein fraction in SOD1 (G93A) mice at late stage but decreased in the detergent-soluble fraction at symptomatic stage. These results suggest that aPKC may be sequestered in SOD1 aggregates, impairing its ability to protect motor neurons from death. Ryk expression was also increased in the motor neurons and the white matter in the ventral lumbar spinal cord of mutant SOD1 mice with a peak at early stage. These observations indicate that Wnt/aPKC and Wnt/Ryk signaling are altered in SOD1 (G93A) mice, suggesting that changed Wnt signaling may contribute to neurodegeneration in ALS.

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Role of Wnt1 and Fzd1 in the spinal cord pathogenesis of amyotrophic lateral sclerosis-transgenic mice

Cited by 32 publications

References 15 publications

Amyotrophic Lateral Sclerosis: Role of the Canonical Wnt/Beta- Catenin Pathway and PPAR Gamma

Amyotrophic Lateral Sclerosis: Role of the Canonical Wnt/Beta- Catenin Pathway and PPAR Gamma

Wnts Are Expressed in the Spinal Cord of Adult Mice and Are Differentially Induced after Injury

Altered expression of atypical PKC and Ryk in the spinal cord of a mouse model of amyotrophic lateral sclerosis

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