Pete Williams
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petetheteapot.bsky.social
Pete Williams
@petetheteapot.bsky.social
1.8K followers 3.5K following 39 posts
Tea drinker and scientist. Neurons, NAD, stuff.

Professor in Vision Science, Research Group Leader - Glaucoma at Karolinska Institutet and St. Erik Eye Hospital, Stockholm (petewilliamslab.com)

CEO - Mim Neurosciences (mimneurosciences.com)
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petetheteapot.bsky.social
Boosting neuronal activity-driven mitochondrial DNA transcription improves cognition in aged mice

www.science.org/doi/10.1126/...

Cool #mitochondria and #aging paper in @science.org
Editor’s summary Aging is associated with impairments in mitochondrial functions. However, how aging affects mitochondria in neurons remains to be fully elucidated. Li et al. examined the role of mitochondrial transcription in learning and memory in the hippocampus of young and aged mice and identified a strong coupling between excitation and mitochondrial transcription (see the Perspective by Bingul and Owen). This process appears to be compromised in aging brains, and increasing its effectiveness counteracted age-dependent cognitive decline in rodents, suggesting a potential target for fighting the cognitive decline associated with aging. —Mattia Maroso
December 31, 2024 at 5:58 PM
petetheteapot.bsky.social
And proof.
Screen clip of the deactivation page
November 17, 2024 at 11:29 AM
petetheteapot.bsky.social
Very interesting!

#NAD #neurodegeneration #NMNAT2 #axonbiology

Transcriptional Regulation of human NMNAT2: Insights from 3D Genome Sequencing and Bioinformatics
www.biorxiv.org/content/10.1...
Nicotinamide mononucleotide adenylyl transferases 2 (NMNAT2) is a crucial nicotinamide adenine dinucleotide (NAD)-synthesizing enzyme essential for neuronal health. In the Religious Orders Study/Memory and Aging Project (ROSMAP), human brain levels of NMNAT2 mRNA positively correlated with cognitive capabilities in older adults. NMNAT2 mRNA abundance is significantly reduced following various insults or proteinopathies. To elucidate the transcriptional regulation of NMNAT2, we employed circular chromosome conformation capture followed by high-throughput sequencing (4C-seq) to identify potential NMNAT2 enhancer and silencer regions by determining genomic regions interacting with the NMNAT2 promoter in human SH-SY5Y cells. We discovered distinct NMNAT2 promoter interactomes in undifferentiated versus neuron-like SH-SY5Y cells. Utilizing bioinformatics analyses, we identified putative transcriptional factors and NMNAT2-associated genes. Notably, the mRNA levels of many of these genes showed a significant correlation with NMNAT2 mRNA levels in single-nuclei RNA-seq datasets from ~400 human subjects in ROSMAP. Additionally, using CRISPR-Cas9 strategies, we confirmed the requirement of two specific genomic regions within the interactomes and four transcription factors in regulating NMNAT2 transcription. In summary, our study identifies genomic loci containing NMNAT2 regulatory elements and predicts associated genes and transcription factors through computational analyses.
November 12, 2024 at 10:26 AM