TGF-β/Smad Signalling in Neurogenesis: Implications for Neuropsychiatric Diseases

Abstract

TGF-β/Smad signalling has been the subject of extensive research due to its role in the cell cycle and carcinogenesis. Modifications to the TGF-β/Smad signalling pathway have been found to produce disparate effects on neurogenesis. We review the current research on canonical and non-canonical TGF-β/Smad signalling pathways and their functions in neurogenesis. We also examine the observed role of neurogenesis in neuropsychiatric disorders and the relationship between TGF-β/Smad signalling and neurogenesis in response to stressors. Overlapping mechanisms of cell proliferation, neurogenesis, and the development of mood disorders in response to stressors suggest that TGF-β/Smad signalling is an important regulator of stress response and is implicated in the behavioural outcomes of mood disorders.

Keywords: TGF-β; depression; neurogenesis; smad; stress.

Figure 1

Illustration of canonical and non-canonical TGF-β signalling. TGF-β ligand binds with TGF-β receptor to form a complex (Created with BioRender.com, accessed on 19 April 2021). The receptor-induced phosphorylation of R-Smads leads to binding with cytoplasmic Smad2/3. Phosphorylated Smads form a complex with Smad4, which translocates to the nucleus where it binds with various transcription factors for gene transcription. Smad complexes initiate a negative feedback loop, leading to Smad7 inhibition of further phosphorylation of R-Smads. TGF-β receptors also phosphorylate TAK1 and CREB, which regulate neuronal differentiation, axonal growth, cell cycle progression, and anti-depressant effects, respectively.