Adam Bachstetter

Spotlight in @cp-immunity.bsky.social
Fibroblasts are not so scar-y in brain injury
www.cell.com/immunity/ful...
on
www.nature.com/articles/s41... @nature.com

With boost to NIH budget, Senate panel rejects Trump’s plan to slash agency Republicans on spending committee push back against proposed reorganization and overhead cuts

The National Institutes of Health’s budget, and structure, would be preserved under a Senate bill for the 2026 fiscal year.

Rising Star at #KSCHIRT: Dr. Catie Profaci (@cprofaci.bsky.social), postdoc in the Patapoutian Lab (@ardemp.bskyverified.social), delivered a standout talk on PIEZO1 mechanosensation in the choroid plexus. Grateful for her visit to Kentucky—excited to follow the work of a true star on the rise!

In-cell architecture of the mitochondrial respiratory chain Mitochondria regenerate adenosine triphosphate (ATP) through oxidative phosphorylation. This process is carried out by five membrane-bound complexes collectively known as the respiratory chain, workin...

In-cell architecture of the mitochondrial respiratory chain

β-hydroxybutyrate facilitates mitochondrial-derived vesicle biogenesis and improves mitochondrial functions Mitochondrial dynamics and metabolites reciprocally influence each other. In this study, Tang et al. discover a role of β-hydroxybutyrate (BHB) in regulating mitochondrial functions. BHB promotes the ...

β-hydroxybutyrate facilitates mitochondrial-derived vesicle biogenesis and improves mitochondrial functions: Molecular Cell www.cell.com/molecular-ce...

Parental origin of transgene modulates amyloid-β plaque burden in the 5xFAD mouse model of Alzheimer’s disease The 5xFAD transgenic model, popular in Alzheimer’s disease research, exhibits varying cerebral plaque burden depending on the parental source of the transgene. Mice inheriting the transgene paternally...

Are you using 5xFAD mice to study Alzheimer’s disease? Our work out today @cp-neuron.bsky.social may be relevant to you 🐁🧠 Age and sex are known to influence Aβ plaque burden in these mice. Here, we found that the transgene parentage is another strong determinant.

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Neurodegeneration in the cortical sulcus is a feature of chronic traumatic encephalopathy and associated with repetitive head impacts - Acta Neuropathologica Neurodegeneration is a seminal feature of many neurological disorders. Chronic traumatic encephalopathy (CTE) is caused by repetitive head impacts (RHI) and is characterized by sulcal tau pathology. H...

link.springer.com/article/10.1...

Amyloid-β and tau deposition in traumatic brain injury: a study of Vietnam War veterans De Bruin et al. report that traumatic brain injury does not inherently elevate the Alzheimer’s pathologies amyloid-β or tau, but is associated with their u

Very happy to share the first PhD work by Hannah de Bruin, showing that traumatic brain injury is not linked to higher fibrillar amyloid and tau per se, but to altered patterns of tau deposition preferentially in TBI vulnerable regions
doi.org/10.1093/brai...
@rikossenkoppele.bsky.social

new preprint!

www.biorxiv.org/content/10.1...

a characterization of APOE effects on the lipid droplet-ome (turns out you see a lot of "AD-related" proteins!)

first authors Cassi Friday & Isaiah Stephens + great collaborators Scott Gordon, @cohenlaboratory.bsky.social @morganti.bsky.social

TREM2 expression level is critical for microglial state, metabolic capacity and efficacy of TREM2 agonism Triggering receptor expressed on myeloid cells 2 (TREM2) is a central regulator of microglial activity and sequence variants are major risk factors for late onset Alzheimer’s disease (LOAD). To better...

A recent preprint from the Haass lab shows that the efficacy of TREM2 agonists in microglia is contingent upon TREM2 expression levels.

Cells with elevated TREM2 expression exhibit reduced responsiveness to agonist treatment.

doi.org/10.1101/2024...

Programming tissue-sensing T cells that deliver therapies to the brain To engineer cells that can specifically target the central nervous system (CNS), we identified extracellular CNS-specific antigens, including components of the CNS extracellular matrix and surface mol...

Simic et al. engineered T cells with synthetic receptors to target brain-localized antigens, activating circuits to kill cancer cells specifically in the brain. Could this precision pave the way for T cell therapies in neurodegenerative diseases?

doi.org/10.1126/scie...

Target-conditioned diffusion generates potent TNFR superfamily antagonists and agonists Despite progress in designing protein-binding proteins, the shape matching of designs to targets is lower than in many native protein complexes, and design efforts have failed for the tumor necrosis f...

Glögl et al. used AI-driven protein design (RFdiffusion) to create selective antagonists for TNFR1, a pro-inflammatory TNF receptor, without targeting the anti-inflammatory TNFR2. This shows the potential of AI tools in therapeutic protein design.

doi.org/10.1126/scie...

Congratulations to Lance Johnson on his excellent talk at the CSHL Neurodegenerative Disease conference on his ApoE switch mice. In my (biased) opinion, it sparked some of the most interesting questions of the meeting!

Ageing limits stemness and tumorigenesis by reprogramming iron homeostasis - Nature Studies using mouse models of lung adenocarcinoma identify an association between age, iron homeostasis and tumour initiation potential that involves NUPR1 and lipocalin-2.

Zhuang et al. show that aging alters iron handling and ferroptosis. Aged cells resist ferroptosis due to reduced iron levels, while young cells rely on iron to maintain stemness. This raises interesting questions about aging and iron regulation in other cell types.

doi.org/10.1038/s415...

β-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain Madhavan et al. identify and characterize the selective regulation of protein solubility by the ketone body β-hydroxybutyrate (βHB) across a range of models. βHB exposure rescues cell-based and C. elegans models of amyloid-β proteotoxicity, and induces clearance of neurodegeneration-related proteins from aged mouse brain following exogenous ketone supplementation.

New paper shows ketones regulate proteostasis. As stated in the paper, “Ketone bodies are janitors of damaged proteins, chaperoning away molecular waste so organisms can operate at peak molecular fitness.”

www.cell.com/cell-chemica...

Hypothalamic deep brain stimulation augments walking after spinal cord injury - Nature Medicine Whole-brain anatomical and activity surveys identify the lateral hypothalamus as a key driver of recovery from spinal cord injury, leading to a deep brain stimulation therapy that augments the recover...

First, in rats (PMID: 22654062); then, in primates (PMID: 27830790); and now in humans (again) nature.com/articles/s41...

This is precisely why we need animal research!

Huge congratulations to the authors on this impressive work!

#Neuroinflammation
Who knew? BTK - it’s not just for #Bcells - check out this study for Brutin’s tyrosine kinase in #microglia and #multiplesclerosis
#neuroskyence #immunosky