title: The therapeutic potential of cell identity reprogramming for the treatment of aging-related neurodegenerative disorders.
abstract: 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.
authors: Department of Molecular Biology, The University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, The University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors: Derek K
authors: DK
authors: Smith
authors: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA; Department of Physical Therapy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors: Miao
authors: M
authors: He
authors: Department of Molecular Biology, The University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, The University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA. Electronic address: Chun-Li.Zhang@UTSouthwestern.edu.
authors: Chun-Li
authors: CL
authors: Zhang
authors: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA; Department of Family Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA; Center for Translational Neurodegeneration and Regenerative Therapy, the Collaborative Innovation Center for Brain Science, Shanghai Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai 200072, China. Electronic address: jzheng@unmc.edu.
authors: Jialin C
authors: JC
authors: Zheng
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D065150:Cellular Reprogramming / Q000187:drug effects / Q000502:physiology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects / Q000502:physiology / Q000637:transplantation*; D019636:Neurodegenerative Diseases / Q000503:physiopathology / Q000628:therapy*
keywords: Alzheimer disease; Amyotrophic lateral sclerosis; Cell identity; Embryonic stem cell; Huntington disease; In vivo reprogramming; Induced neural stem cell; Induced pluripotent stem cell; Neural stem cell; Neurodegeneration; Neuron; Parkinson disease; Regenerative medicine; Reprogramming; Stem cell; Transdifferentiation