Inhibition of the canonical Wnt pathway by Dickkopf-1 contributes to the neurodegeneration in 6-OHDA-lesioned rats

Dun, Yaoyan; Li, Gang; Yang, Yang; Xiong, Zhengguo; Feng, Mei; Wang, Min; Zhang, Yuan; Xiang, Jizhou; Ma, Rong

doi:10.1016/j.neulet.2012.07.030

Cited by 49 publications

(44 citation statements)

References 41 publications

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“…Mutated VPS35 may, therefore, lead to divalent metal transporter 1 missorting and iron accumulation, similar to the iron accumulation described in PD patients and in the 6-OHDA mouse model of PD [225]. Finally, VPS35 is also hypothesized to influence the Wnt signaling pathway via deficient sorting of the Wntless protein, which leads to Wntless degradation [226][227][228] and Wnt/b-catenin signaling is impaired in 6-OHDA-lesioned rats [229] and MPTP-induced mouse and monkey models [230].…”

Section: Vps35 (Park17)mentioning

confidence: 71%

Neural stem cells in Parkinson’s disease: a role for neurogenesis defects in onset and progression

Grand

Gonzalez-Cano

Pavlou

et al. 2014

Cell. Mol. Life Sci.

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Parkinson's disease (PD) is the second most common neurodegenerative disorder, leading to a variety of motor and non-motor symptoms. Interestingly, nonmotor symptoms often appear a decade or more before the first signs of motor symptoms. Some of these non-motor symptoms are remarkably similar to those observed in cases of impaired neurogenesis and several PD-related genes have been shown to play a role in embryonic or adult neurogenesis. Indeed, animal models deficient in Nurr1, Pitx3, SNCA and PINK1 display deregulated embryonic neurogenesis and LRRK2 and VPS35 have been implicated in neuronal development-related processes such as Wnt/bcatenin signaling and neurite outgrowth. Moreover, adult neurogenesis is affected in both PD patients and PD animal models and is regulated by dopamine and dopaminergic (DA) receptors, by chronic neuroinflammation, such as that observed in PD, and by differential expression of wild-type or mutant forms of PD-related genes. Indeed, an increasing number of in vivo studies demonstrate a role for SNCA and LRRK2 in adult neurogenesis and in the generation and maintenance of DA neurons. Finally, the roles of PDrelated genes, SNCA, LRRK2, VPS35, Parkin, PINK1 and DJ-1 have been studied in NSCs, progenitor cells and induced pluripotent stem cells, demonstrating a role for some of these genes in stem/progenitor cell proliferation and maintenance. Together, these studies strongly suggest a link between deregulated neurogenesis and the onset and progression of PD and present strong evidence that, in addition to a neurodegenerative disorder, PD can also be regarded as a developmental disorder.

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Section: Vps35 (Park17)mentioning

confidence: 71%

Neural stem cells in Parkinson’s disease: a role for neurogenesis defects in onset and progression

Grand

Gonzalez-Cano

Pavlou

et al. 2014

Cell. Mol. Life Sci.

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“…The findings of Zhou et al demonstrated that ginsenoside Rg1 exerts anti-apoptotic function in an in vitro model of PD, which may be achieved by activating the Wnt/β-catenin signaling pathway [34]. The inhibition of the Wnt/β-catenin signaling cascade by DKK-1 aggravates the dopaminergic neuron damage in the substantia nigra region and leads to degeneration in 6-OHDA-lesioned neurons [35]. …”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Curcumin Against Oxidative Stress-Induced Injury in Rats with Parkinson’s Disease Through the Wnt/ β-Catenin Signaling Pathway

Wang

Zhang

et al. 2017

Cell Physiol Biochem

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Background/Aims: The study aimed to investigate the protective effect of curcumin against oxidative stress-induced injury of Parkinson’s disease (PD) through the Wnt/β-catenin signaling pathway in rats. Methods: The successfully established PD rat models and normal healthy rats were randomly assigned into the 6-hydroxydopamine (6-OHDA), the curcumin (Cur) and the control groups. Immunohistochemistry was used to detect the positive expression of tyrosine hydroxylase (TH), dopamine transporter (DAT) and glial fibrillary acidic protein (GFAP). Deutocerebrum primary cells were extracted and classified into the control, 6-OHDA, Cur (5, 10, 15 µmol/L), Dickkopf-1 (DKK-1) and Cur + DKK-1 groups. MTT assays, adhesion tests and TUNEL staining were used to assess cell viability, adhesion and apoptosis, respectively. Western blotting and qRT-PCR were used to examine the protein and mRNA expressions of Wnt3a and β-catenin and the c-myc and cyclinD1 mRNA expressions. Results: TH and DAT expressions in the Cur group were elevated and GFAP was reduced compared with the 6-OHDA group. Curcumin enhanced viability, survival and adhesion and attenuated apoptosis of deutocerebrum primary cells by activating the Wnt/β-catenin signaling pathway. Higher Wnt3a and β-catenin mRNA and protein expressions and c-myc and cyclinD1 mRNA expressions, enhanced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) contents, decreased malondialdehyde (MDA) content and elevated mitochondrial membrane potential (∆ψm) were found in the 10 and 15 µmol/L Cur groups compared with the 6-OHDA group. However, opposite tendencies were found in the Cur + DKK-1 group compared to the 10 µmol/L Cur group. Conclusion: This study suggests that curcumin could protect against oxidative stress-induced injury in PD rats via the Wnt/β-catenin signaling pathway.

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“…Dkk-1 is the most important family member and has been largely investigated in recent years [20]. The expression level of Dkk-1 remains very low in the normal adult brain, but is upregulated after brain insults [22][23][24]. Dkk-1 is a high-affinity ligand for LRP5/6 and prevents Fz-LRP5/6 complex formation, thus inhibiting downstream signaling [25].…”

Section: Wnt/b-catenin Signaling Pathwaymentioning

confidence: 99%

The Role of Wnt/β-Catenin Signaling Pathway in Disrupted Hippocampal Neurogenesis of Temporal Lobe Epilepsy: A Potential Therapeutic Target?

Huang

Zhou

et al. 2015

Neurochem Res

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Temporal lobe epilepsy is one of the most common clinical neurological disorders. One of the major pathological findings in temporal lobe epilepsy is hippocampal sclerosis, characterized by massive neuronal loss and severe gliosis. The epileptogenesis process of temporal lobe epilepsy usually starts with initial precipitating insults, followed by neurodegeneration, abnormal hippocampus circuitry reorganization, and the formation of hypersynchronicity. Experimental and clinical evidence strongly suggests that dysfunctional neurogenesis is involved in the epileptogenesis. Recent data demonstrate that neurogenesis is induced by acute seizures or precipitating insults, whereas the capacity of neuronal recruitment and proliferation substantially decreases in the chronic phase of epilepsy. Participation of the Wnt/β-catenin signaling pathway in neurogenesis reveals its importance in epileptogenesis; its dysfunction contributes to the structural and functional abnormality of temporal lobe epilepsy, while rescuing this pathway exerts neuroprotective effects. Here, we summarize data supporting the involvement of Wnt/β-catenin signaling in the epileptogenesis of temporal lobe epilepsy. We also propose that the Wnt/β-catenin signaling pathway may serve as a promising therapeutic target for temporal lobe epilepsy treatment.

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Inhibition of the canonical Wnt pathway by Dickkopf-1 contributes to the neurodegeneration in 6-OHDA-lesioned rats

Cited by 49 publications

References 41 publications

Neural stem cells in Parkinson’s disease: a role for neurogenesis defects in onset and progression

Neural stem cells in Parkinson’s disease: a role for neurogenesis defects in onset and progression

Protective Effect of Curcumin Against Oxidative Stress-Induced Injury in Rats with Parkinson’s Disease Through the Wnt/ β-Catenin Signaling Pathway

The Role of Wnt/β-Catenin Signaling Pathway in Disrupted Hippocampal Neurogenesis of Temporal Lobe Epilepsy: A Potential Therapeutic Target?

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