Neural Therapies

Unlocking Microglial Secrets in Neurodegeneration Dark microglia, which are abundant in Alzheimer’s disease patients, have long been associated with aging and neurodegeneration. In a recent Neuron article (February 19, 2025), Flury et al. describe a stress response pathway in this microglial subset that triggers neurodegenerative effects such as synapse loss. In Alzheimer’s disease models, activation of this pathway exacerbates neurodegeneration, while its inhibition ameliorates these effects. Their  “in vitro” assays reveal that the integrated stress response prompts microglia to secrete toxic lipids that impair neuronal homeostasis and survival. https://lnkd.in/ds_6g9qZ

Looking for Tools Against Parkinson's Disease Parkinson’s disease is a neurodegenerative disorder associated with inflammation, which is mainly mediated by microglial activation. In a recent study in the Journal of Neuroinflammation (February 2025), Leser et al. describe the role of the neuronal chemokine CCL21 through the CCR7 receptor in regulating microglial behavior. Dopaminergic neurons of the substantia nigra (one of the brain regions that degenerates in PD) overexpress CCL21, thus promoting neuroinflammation. In experiments using mouse models of PD, treatment with navarixin, a CCR7 inhibitor, blocks the effects of CCL21 and prevents neurodegeneration and cognitive decline, opening up potential new strategies for the treatment of PD. https://lnkd.in/dCjzc5jy

Modulating Inflammation as a Clue for Healthy Aging? In a recent study in Brain 148(2):480-492 (February 2025), Cai et al report the relationships between inflammatory markers in the blood change with age and their relationship to Alzheimer's diseas and other dementias. The study revealed that certain inflammatory markers, such as complement C3, interleukin-1β, and interleukin-6, increase before Alzheimer's symptoms appear. Notably, complement C3 seems specifically linked to Alzheimer's, while the other two markers are also associated with other dementias. These results suggest that managing inflammation could be crucial for healthy aging and for preventing or treating Alzheimer's disease. https://lnkd.in/dQPXnme2

Modifying the Human Pluripotent Stem Cell State by Intercellular mRNA Transfer In a recent PNAS report (January 22, 2025), Yoneyama et al. describe that in cocultures of mouse embryonic stem cells with human primed pluripotent stem cells (hPSCs), direct cell-to-cell contact enables the transfer of mRNA**. This transfer allows cell reprogramming without the need for nuclear transfer or cell fusion, providing new insights into both intra- and interspecies cellular communication. https://lnkd.in/dZcmh_qg

Fighting Inflammation: A Putative Tool Against Alzheimer’s Disease Brain inflammation, characterized by an increased density of microglia and macrophages, is a significant component of Alzheimer’s disease (AD) and represents a promising therapeutic target. In a recent study published in Brain (January 2025), Appleton et al. reported the presence of inflammation in mild cognitive impairment associated with early-onset Alzheimer’s disease. Their findings indicate a correlation between inflammation and the presence of beta-amyloid and tau in brain regions such as the precuneus, lateral temporal and temporal association areas, and the right amygdala. The study further suggests that tau propagation in humans is closely linked to brain inflammation, emphasizing the potential of targeting inflammation as a therapeutic approach in the progression of AD. https://lnkd.in/dujWFWey

Developing Specific Transcriptomic Databases for Nervous System Cell Populations Cahoy et al., in the Journal of Neuroscience (January 20th, 2025), describe methods for isolating and purifying astrocytes, neurons, and oligodendrocytes from the developing and mature mouse forebrain. Using fluorescent-activated cell sorting, the authors isolated astrocytes from transgenic mice expressing enhanced green fluorescent protein (EGFP) under the S100β promoter. They then created a transcriptome database by profiling the gene expression of over 20,000 genes in these three cell types at various postnatal ages (P1 to P30). This database offers a detailed comparison of gene expression in astrocytes, neurons, and oligodendrocytes. Key findings include the identification of Aldh1L1 as a highly specific marker for astrocytes, as well as the enrichment of astrocytes in metabolic, lipid synthetic, and phagocytic pathways. These findings challenge the traditional classification of glial cells, highlighting the distinct gene profiles of astrocytes and oligodendrocytes. The transcriptome database provides valuable resources for understanding neural development, function, and disease. https://lnkd.in/daMFAi9G

Congratulations to Alba Puente, who yesterday obtained her PhD degree with International and Industrial Mentions! She conducted her doctoral thesis at Neural Therapies SL under an Industrial Program grant from the Ministerio de Ciencia, Innovación y Universidades (reference 2018-010144). We are proud that she has achieved this milestone within our enterprise.

Reviewing Neurovascular Aging In a recent article in Neuron (January 8, 2025), Santisteban and Iadecola review the pathology of neurovascular aging, emphasizing its significance in brain aging and disease risk. The authors highlight that neurovascular aging diminishes the delivery of oxygen and glucose, impairs endothelial transport, and disrupts the blood-brain exchange. These changes lead to imbalances in protein homeostasis, reduced clearance of waste and toxic proteins, weakened immunoprivilege status, and a decrease in critical nervous system growth factors. The review also examines the effects of neurovascular aging on conditions such as stroke and Alzheimer's disease and addresses challenges associated with using pharmacological agents to mitigate brain aging and related diseases. A comprehensive and insightful review highly recommended for those interested in the aging brain. https://lnkd.in/dijQ3T5Z

Reviewing Clinical Trials with Pluripotent Stem Cells In the first issue of 2025 of Cell Stem Cell, Kirkeby et al. review clinical trials involving human pluripotent stem cells (hPSCs), focusing on the available data regarding their safety and efficacy in clinical settings. They identify 116 clinical trials up to December 2024, testing 83 hPSC products. Most of these trials target the eye, central nervous system, and cancer. The authors report that more than 1,200 patients have been dosed with hPSC products, with no generalizable safety concerns observed to date. https://lnkd.in/dFz4d-MK

Reaching Nanometer Resolution in Biological Tissues Minimal photon fluxes (MINFLUX) nanoscopy is an emerging optical imaging technique that enables the visualization of biological molecules with nanometer-scale resolution. Although it has primarily been applied in cultured cells, a recent article by Moosmayer et al., published in PNAS (December 2024), demonstrates its application in localizing synaptic molecules in mouse brain tissue. The authors report achieving single-fluorophore localization with a precision of <5 nm at sample depths of up to 80 µm in brain tissue sections. Notably, they mapped PSD95 localization relative to spine head morphology, while simultaneously visualizing the presynaptic glutamate transporter (VGLUT1) and the postsynaptic glutamate channel receptor AMPAR. https://lnkd.in/dF5iz4MG