查看更多>>摘要：Neurons are believed to be non-proliferating cells.However,neuronal stem cells are still pre-sent in certain areas of the adult brain,although their proliferation diminishes with age.Just as with other cells,their proliferation and differentiation are modulated by various mechanisms.These mechanisms are foundational to the strategies developed to induce neuronal proliferation and differentiation,with poten-tial therapeutic applications for neurodegenerative diseases.The most common among these diseases are Parkinson's disease and Alzheimer's disease,associated with the formation of β-amyloid(Aβ)aggregates which cause a reduction in the number of neurons.Compounds such as LiCl,4-aminothiazoles,Pregnen-olone,ACEA,harmine,D2AAK1,methyl 3,4-dihydroxybenzoate,and shikonin may induce neuronal proliferation/differentiation through the activation of pathways:MAPK ERK,PI3K/AKT,NFκB,Wnt,BDNF,and NPAS3.Moreover,combinations of these compounds can potentially transform somatic cells into neurons.This transformation process involves the activation of neuron-specific transcription factors such as NEUROD1,NGN2,ASCL1,and SOX2,which subsequently leads to the transcription of down-stream genes,culminating in the transformation of somatic cells into neurons.Neurodegenerative dis-eases are not the only conditions where inducing neuronal proliferation could be beneficial.Consequently,the impact of pro-proliferative compounds on neurons has also been researched in mouse models of Alzheimer's disease.
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