Role of Wnt Signaling in Adult Hippocampal Neurogenesis in Health and Disease

Abstract

Neurogenesis persists during adulthood in the dentate gyrus of the hippocampus. Signals provided by the local hippocampal microenvironment support neural stem cell proliferation, differentiation, and maturation of newborn neurons into functional dentate granule cells, that integrate into the neural circuit and contribute to hippocampal function. Increasing evidence indicates that Wnt signaling regulates multiple aspects of adult hippocampal neurogenesis. Wnt ligands bind to Frizzled receptors and co-receptors to activate the canonical Wnt/β-catenin signaling pathway, or the noncanonical β-catenin-independent signaling cascades Wnt/Ca 2+ and Wnt/planar cell polarity. Here, we summarize current knowledge on the roles of Wnt signaling components including ligands, receptors/co-receptors and soluble modulators in adult hippocampal neurogenesis. Also, we review the data suggesting distinctive roles for canonical and non-canonical Wnt signaling cascades in regulating different stages of neurogenesis. Finally, we discuss the evidence linking the dysfunction of Wnt signaling to the decline of neurogenesis observed in aging and Alzheimer's disease.

Neuroprotective Activities of Curcumin in Parkinson’s Disease: A Review of the Literature

“…Furthermore, curcumin antioxidant activities restored dopamine as well as tyrosine hydroxylase levels in an MPTP model of PD [ 95 ]. One of the main elements in the development of the nervous system and regulation of brain neurogenesis is the activation of the Wnt/β-catenin signaling pathway [ 96 ]. Curcumin has been shown to protect against oxidative stress-induced neurodegeneration in 6-OHDA PD by stimulating the Wnt/β-catenin pathway, which consequently leads to improving cell viability, survival, and reducing neuronal apoptosis [ 97 ].…”

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

“…The canonical Wnt/β-catenin signaling pathway is a pivotal pathway that plays an evident role in promoting tissue repair and regulating stem cell activity, including NSCs proliferation and differentiation, when activated after brain injury (Ding et al, 2011 ; Arredondo et al, 2020 ; Marchetti et al, 2020 ). Meanwhile, Studies also represent that elevated β-catenin expression via activating Wnt/β-catenin signaling pathway not only regulates NSCs proliferation and differentiation, but also promotes neuron survival in cerebral diseases, including Parkinson's disease, Alzheimer's disease, and ischemic stroke (Marchetti, 2018 ; Qiu et al, 2019 ; Zhang et al, 2019 ; Arredondo et al, 2020 ). Furthermore, previous reports have indicated that Wnt/β-catenin signaling pathway and its downstream effectors are associated with neuroinflammation to regulate demyelination and remyelination in developing brain and Multiple Sclerosis (MS) (Vallée et al, 2018 ; Van Steenwinckel et al, 2019 ).…”

Convergent Canonical Pathways in Autism Spectrum Disorder from Proteomic, Transcriptomic and DNA Methylation Data

“…Previous reviews have comprehensively described the role of mTORC1 signalling in protein synthesis, neuronal differentiation, migration, and patterning [ 57 ], but these reviews have focused less on the role of mTORC1 as a regulator of mitochondrial metabolism. The same is true for reviews on the role played by WNT signalling in neurogenesis and ASD [ 159 , 160 ], which describe the central role played by WNT signalling in NSC proliferation and differentiation. However, our review emphasises how WNT-PPARGy signalling intersects with PPARGC1A, anti-inflammatory and antioxidant responses, and the regulation of mitochondrial biogenesis and metabolism.…”