The capacity for neurogenesis in the adult mammalian brain is extremely limited and highly restricted to a few regions, which greatly hampers neuronal regeneration and functional restoration after neuronal loss caused by injury or disease. Meanwhile, transplantation of exogenous neuronal stem cells into the brain encounters several serious issues including immune rejection and the risk of tumorigenesis. Recent discoveries of direct reprogramming of endogenous glial cells into functional neurons have provided new opportunities for adult neuro-regeneration. Here, we extensively review the experimental findings of the direct conversion of glial cells to neurons in vitro and in vivo and discuss the remaining issues and challenges related to the glial subtypes and the specificity and efficiency of direct cell-reprograming, as well as the influence of the microenvironment. Although in situ glial cell reprogramming offers great potential for neuronal repair in the injured or diseased brain, it still needs a large amount of research to pave the way to therapeutic application.
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http://dx.doi.org/10.1007/s12264-021-00751-3 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Department of Cell Biology, Emory University, Atlanta, GA 30322.
To regulate brain function, peripheral compounds must traverse the blood-brain barrier (BBB), an interface between the brain and the circulatory system. To determine whether specific transport mechanisms are relevant for sleep, we conducted a BBB-specific inducible RNAi knockdown (iKD) screen for genes affecting sleep in . We observed reduced sleep with knockdown of solute carrier , a carnitine transporter, as determined by isotope flux.
View Article and Find Full Text PDFCell Biol Toxicol
January 2025
Department of Environmental Medicine, School of Medicine, Chongqing University, Chongqing, China.
Manganese (Mn) is a neurotoxin that has been etiologically linked to the development of neurodegenerative diseases in the case of overexposure. It is widely accepted that overexposure to Mn leads to manganism, which has clinical symptoms similar to Parkinson's disease (PD), and is referred to as parkinsonism. Astrocytes have been reported to scavenge and degrade extracellular α-synuclein (α-Syn) in the brain.
View Article and Find Full Text PDFBull Math Biol
January 2025
Bioinformatics and Computational Biology Program, Worcester Polytechnic Institute, Worcester, MA, USA.
Neuroinflammation immediately follows the onset of ischemic stroke in the middle cerebral artery. During this process, microglial cells are activated in and recruited to the penumbra. Microglial cells can be activated into two different phenotypes: M1, which can worsen brain injury; or M2, which can aid in long-term recovery.
View Article and Find Full Text PDFMedicines (Basel)
January 2025
Laboratory of Molecular Neurology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan.
Introduction: In the central nervous system (CNS), proper interaction between neuronal and glial cells is crucial for the development of mature nervous tissue. Hypomyelinating leukodystrophies (HLDs) are a group of genetic CNS disorders characterized by hypomyelination and/or demyelination. In these conditions, genetic mutations disrupt the biological functions of oligodendroglial cells, which are responsible for wrapping neuronal axons with myelin sheaths.
View Article and Find Full Text PDFNoncoding RNA
January 2025
Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE), 37075 Göttingen, Germany.
Aging leads to cognitive decline and increased risk of neurodegenerative diseases. While molecular changes in central nervous system (CNS) cells contribute to this decline, the mechanisms are not fully understood. Long non-coding RNAs (lncRNAs) are key regulators of cellular functions.
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