FAD Influx Enhances Neuronal Differentiation Of Human Neural Stem Cells By Facilitating Nuclear Loc

Terma

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Some neat studies from 2017:
FAD influx enhances neuronal differentiation of human neural stem cells by facilitating nuclear localization of LSD1
FAD influx enhances neuronal differentiation of human neural stem cells by facilitating nuclear localization of LSD1
Flavin adenine dinucleotide (FAD), synthesized from riboflavin, is redox cofactor in energy production and plays an important role in cell survival. More recently, riboflavin deficiency has been linked to developmental disorders, but its role in stem cell differentiation remains unclear. Here, we show that FAD treatment, using DMSO as a solvent, enabled an increase in the amount of intracellular FAD and promoted neuronal differentiation of human neural stem cells (NSCs) derived not only from fetal brain, but also from induced pluripotent stem cells. Depression of FAD‐dependent histone demethylase, lysine‐specific demethylase‐1 (LSD1), prevented FAD‐induced neuronal differentiation. Furthermore, FAD influx facilitated nuclear localization of LSD1 and its enzymatic activity. Together, these findings led us to propose that FAD contributes to proper neuronal production from NSCs in the human fetal brain during development.
(note: contrary to popular observations, demethylation of some histones acts to repress gene transcription)

LSD1 protects against hippocampal and cortical neurodegeneration
LSD1 protects against hippocampal and cortical neurodegeneration
To investigate the mechanisms that maintain differentiated cells, here we inducibly delete the histone demethylase LSD1/KDM1A in adult mice. Loss of LSD1 leads to paralysis, along with widespread hippocampus and cortex neurodegeneration, and learning and memory defects. We focus on the hippocampus neuronal cell death, as well as the potential link between LSD1 and human neurodegenerative disease and find that loss of LSD1 induces transcription changes in common neurodegeneration pathways, along with the re-activation of stem cell genes, in the degenerating hippocampus. These data implicate LSD1 in the prevention of neurodegeneration via the inhibition of inappropriate transcription. Surprisingly, we also find that transcriptional changes in the hippocampus are similar to Alzheimer’s disease (AD) and frontotemporal dementia (FTD) cases, and LSD1 is specifically mislocalized to pathological protein aggregates in these cases. These data raise the possibility that pathological aggregation could compromise the function of LSD1 in AD and FTD.

Traditionally the major factor in proper differentiation is Retinoic acid and some growth factors, but from these studies it's apparent that a B2/FAD deficiency will completely ruin differentiation through preventing LSD1 (LSD1 is the metabolic opposite to SIRT1). By extension low thyroxin will as well. Will refrain from a series of further obvious observations.

Also, I did not know you could carry preformed FAD in DMSO, hmmm...
 
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