The role of transforming growth factor β1 /Smad pathway in Alzheimer's disease inflammation pathology

Alzheimer's disease (AD), a progressive disorder, has become a global health problem and is now the main cause of dementia. The aetiology of AD is complex and remains elusive making effective AD treatment difficult. Current drugs for AD only improve symptoms but do not interfere with pathogenic mechanisms. Three main hypotheses have been brought forward regarding AD aetiology, one of them being the 'inflammation hypothesis'. A number of studies have demonstrated that inflammation plays a critical role in AD. Self-limiting neuroinflammation is considered beneficial to AD, whereas chronic inflammation aggravates brain injury and neuronal death. Transforming growth factor β 1(TGF-β1) is an anti-inflammatory cytokine with neuroprotective properties. Smad proteins are downstream molecules of TGF-β signalling. They are cytoplasmic transcription factors that can regulate targeted gene expression. In AD, impairments of TGF-β1/Smad pathways have been observed. Moreover, microglia, astrocytes, inflammasomes, and insulin resistance also have been implicated in AD pathogenesis. Elucidating the molecular mechanisms underlying AD pathogenesis is a fundamental step toward designing new treatment options. In this review, we detail the changes in TGF-β1/Smad pathways in AD and hope this will facilitate further research on AD treatment.