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Direct reprogramming of terminally differentiated cells into neurons: A novel and promising strategy for Alzheimer's disease treatment

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PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pnpbp.2019.109820

Keywords

Alzheimer's disease; Glial cells; Neural repair; Reprogramming; Neuron

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Glial activation is a common pathological process of the central nervous system (CNS) in disorders such as Alzheimer's disease (AD). Several approaches have been used to reduce the number of activated astrocytes and microglia in damaged areas. In recent years, various kinds of fully differentiated cells have been successfully reprogrammed to a desired type of cell in lesion areas. Interestingly, internal glial cells, including astrocytes and NG2 positive cells, were efficiently converted to neuroblasts and neurons by overexpression of some transcription factors (TFs) or microRNAs (miRNAs). Notably, some specific subtypes of neurons have been achieved by in vivo reprogramming and the resulting neurons were successfully integrated into local neuronal circuits. Furthermore, somatic cells from AD patients have been converted to functional neurons. Although direct reprogramming of a patient's own internal cells has revolutionized regenerative medicine, but there are some major obstacles that should be examined before using these induced cells in clinical therapies. In the present review article, we aim to discuss the current studies on in vitro and in vivo reprogramming of somatic cells to neurons using TFs, miRNAs or small molecules in healthy and AD patients.

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