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

Abstract

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.

Ambroxol Upregulates Glucocerebrosidase Expression to Promote Neural Stem Cells Differentiation Into Neurons Through Wnt/β-Catenin Pathway After Ischemic Stroke

“…The canonical Wnt/βcatenin pathway, one of the highly conserved developmental pathways, plays a pivotal role in various physical and pathological conditions, including regulation of neurogenesis, tissue homeostasis and neural survival in the nervous system (CNS) (Weimar et al, 2002;Marchetti and Pluchino, 2013;Zheng et al, 2017;Marchetti, 2018;Gao et al, 2020). Especially, the homeostasis between unactive state of Wnt/β-catenin pathway and active condition of Wnt/β-catenin pathway dynamically regulates the survival, proliferation, and differentiation of NSCs (Awad et al, 2017;Gao et al, 2020). Inactivation of Wnt/β-catenin pathway induces β-Catenin degradation in the cytoplasm via phosphorylation and ubiquitination by glycogen synthase kinase 3 (GSK3) and casein kinase 1 (CK1) (Jho et al, 2002;Gao et al, 2020).…”

LINC01128 regulates the development of osteosarcoma by sponging miR‐299‐3p to mediate MMP2 expression and activating Wnt/β‐catenin signalling pathway

“…Wnt/β‐catenin signalling is an evolutionarily conserved and versatile pathway. Several studies have implicated the Wnt/β‐catenin pathway in tissue homeostasis, embryonic development and various human diseases 34‐36 . Ectopic activation of this pathway leads to the accumulation of β‐catenin in the nucleus and stimulates the transcription of many oncogenes 37,38 .…”

Glia and Neural Stem and Progenitor Cells of the Healthy and Ischemic Brain: The Workplace for the Wnt Signaling Pathway

“…Adult NSCs undergo asymmetric division to maintain a pool of pluripotent cells, while providing progenitor cells capable of differentiating to neuronal and glial cell populations. Recent studies provide evidence that these processes require precise regulation of molecular signals in order to prevent the gradual loss of postnatal NSCs, and ensure continuous neurogenesis in the brain (reviewed in Reference [23]).…”

“…As a component of a protein complex with cadherins, the protein forms adherent junctions [ 20 ], while in a complex with α-catenin, it also interacts with the cytoskeleton [ 21 ]. On the other hand, free cytoplasmic β-catenin acts as an intracellular signal transducer in order to influence gene transcription [ 22 ], and exerts its full influence on the self-renewal and proliferation of NS/PCs [ 23 ]. In the absence of a Wnt signal, a multi-component, so-called β-catenin destruction complex is formed in the cytoplasm.…”