Hippocampal neurogenesis plays a critical role in the formation of new neurons during learning and memory development. Attenuation of neurogenesis in the brain is one of the primary causes of dementia in Alzheimer’s disease (AD), and, conversely, modulating the process of hippocampal neurogenesis benefit patients with AD. Traditional Chinese medicine (TCM), particularly herbal medicine, has been in use for thousands of years in Asia and many regions of the world for the treatment of cancer, cardiovascular diseases and neurodegenerative diseases. In this review, we summarize the role of neurotrophic factors, signal transducing factors, epigenetic modulators and neurotransmitters in neurogenesis, and we also discuss the functions of several Chinese herbs and their active molecules in activating multiple pathways involved in neurogenesis. TCM herbs target pathways such as Notch, Wnt, Sonic Hedgehog and receptor tyrosine kinase pathway, leading to activation of a signaling cascade that ultimately enhances the transcription of several important genes necessary for neurogenesis. Given these pathway activating effects, the use of TCM herbs could be an effective therapeutic strategy for the treatment of AD.

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases in older individuals with specific neuropsychiatric symptoms. It is a proteinopathy, pathologically characterized by the presence of misfolded protein (Aβ and Tau) aggregates in the brain, causing progressive dementia. Increasing studies have provided evidence that the defect in protein-degrading systems, especially the autophagy-lysosome pathway (ALP), plays an important role in the pathogenesis of AD. Recent studies have demonstrated that AD-associated protein aggregates can be selectively recognized by some receptors and then be degraded by ALP, a process termed aggrephagy. In this study, we reviewed the role of aggrephagy in AD development and discussed the strategy of promoting aggrephagy using small molecules for the treatment of AD.

TFEB (transcription factor EB), which is a master regulator of autophagy and lysosome biogenesis, is considered to be a new therapeutic target for Parkinson’s disease (PD). However, only several small-molecule TFEB activators have been discovered and their neuroprotective effects in PD are unclear. In this study, a curcumin derivative, named E4, was identified as a potent TFEB activator. Compound E4 promoted the translocation of TFEB from cytoplasm into nucleus, accompanied by enhanced autophagy and lysosomal biogenesis. Moreover, TFEB knockdown effectively attenuated E4-induced autophagy and lysosomal biogenesis. Mechanistically, E4-induced TFEB activation is mainly through AKT-MTORC1 inhibition. In the PD cell models, E4 promoted the degradation of α-synuclein and protected against the cytotoxicity of MPP⁺ (1-methyl-4-phenylpyridinium ion) in neuronal cells. Overall, the TFEB activator E4 deserves further study in animal models of neurodegenerative diseases, including PD.