The therapeutic potential of cell identity reprogramming for the treatment of aging-related neurodegenerative disorders

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HIGHLIGHTSNeural reprogramming aims to reconstruct neural networks destroyed by neurodegenerative disease.Neuron transplantation and in vivo transdifferentiation enable functional recovery.iPSCs enable in vitro modeling of neurodegeneration.Clinical application of reprogramming technologies faces six general obstacles.Neural cell identity reprogramming strategies aim to treat age-related neurodegenerative disorders with newly induced neurons that regenerate neural architecture and functional circuits in vivo. The isolation and neural differentiation of pluripotent embryonic stem cells provided the first in vitro models of human neurodegenerative disease. Investigation into the molecular mechanisms underlying stem cell pluripotency revealed that somatic cells could be reprogrammed to induced pluripotent stem cells (iPSCs) and these cells could be used to model Alzheimer disease, amyotrophic lateral sclerosis, Huntington disease, and Parkinson disease. Additional neural precursor and direct transdifferentiation strategies further enabled the induction of diverse neural linages and neuron subtypes both in vitro and in vivo. In this review, we highlight neural induction strategies that utilize stem cells, iPSCs, and lineage reprogramming to model or treat age-related neurodegenerative diseases, as well as, the clinical challenges related to neural transplantation and in vivo reprogramming strategies.

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