A pathogenic Tau mutation drives autophagy-lysosome dysfunction that limits Tau degradation in a model of frontotemporal dementia - Nature Communications Researchers show that a disease-causing Tau mutation disrupts the autophagy-lysosome pathway in human neurons, leading to Tau accumulation, and that enhancing autophagy can partially restore protein c...

1/6 Can a single Tau mutation break the neuron’s recycling system? 🧠🔬
Our new study in Nature Communications links p.R406W Tau to multi-step autophagy failure, and points to a therapeutic path.
#Tauopathies #endFTD #DrugDiscovery #Neuroscience #Lysosomes www.nature.com/articles/s41...

Images showing how expressing human Tau in the Drosophila wing reduces the size of the posterior compartment. Panels include: a schematic of larval and adult wings highlighting the posterior region; fluorescent wing discs expressing control mCD8::Cherry or mCherry‑tagged human Tau with E‑cadherin staining; quantification plots comparing posterior/anterior size ratios; and adult wings with the posterior compartment outlined, demonstrating that Tau isoforms 0N4R and 2N4R significantly shrink this region.

@miguelrmphd.bsky.social, Douglas Watt Allan, Amritpal Mudher & co model Tau-induced neurotoxicity in the #Drosophila wing, enabling a rapid, genetically tractable in vivo system for #tauopathies studies.

Read doi.org/10.1242/dmm....

@sotonbiosciences.bsky.social @unisouthampton.bsky.social

Die Moleküle des Vergessens - Wie experimentelle menschliche Gehirnzellen den Weg zu Demenztherapien ebnen können Angelika Dannert, PhD, Ludwig-Maximilians-Universität München

Angelika developed a novel #iPSC model of #Tauopathies, a group of dementias including #Alzheimer's disease. 🧠 More here (in German): koerber-stiftung.de/en/projects/...

5/5 In summary, SNHG8 and FAM151B‑DT play complementary roles in tauopathies: SNHG8 limits stress granules that drive tau aggregation, while FAM151B‑DT enhances clearance of toxic proteins, opening new paths for understanding and treating tau-related disease. 🧫🔬🧐
#Neuroscience #Tauopathies #endFTD

4/5 SNHG8 and FAM151B-DT help neurons manage stress and clear toxic proteins. Low SNHG8 boosts stress granules, while FAM151B-DT links tau, α-synuclein & HSC70 to enhance autophagy, together protecting cells from tau-related damage. 👩‍🔬👨🏾‍🔬
#Neuroscience #Tauopathies #endFTD

3/5 Both SNHG8 and FAM151B-DT are reduced in neurons with pathogenic MAPT mutations and in brains from patients with tauopathies such as FTLD, PSP, and AD, linking these lncRNAs broadly to tau-related neurodegeneration. 🧠🧪
#Neuroscience #Tauopathies #endFTD

2/5 SNHG8 and FAM151B DT are key targets to restore protein balance and reduce toxic protein buildup in neurodegenerative diseases. Promising steps toward new therapies! 🔬🥼🧫 #Tauopathies #endFTD

1/5 Hey friends! Exciting news! Two new studies highlight the role of lncRNAs SNHG8 & FAM151B DT in tau-related brain disorders. These discoveries open new paths for research & therapy. 🔬📚 #Tauopathies #endFTD
Read more:
🔗 pubmed.ncbi.nlm.nih.gov/37730840/
🔗 pubmed.ncbi.nlm.nih.gov/41053434/

Strategies For Complicated Neurodegenerative Disorders - Dr. Leonard Petrucelli - Department of Neuroscience, Mayo Clinic on Progress, Potential, And Possibilities #Tauopathies #ProgressiveSupranuclearPalsy #FrontotemporalDementia #RichardRainwater #BruceWillis - www.youtube.com/watch?v=hxOc...

Check out part 3 of 3 of our new blog on the "Single-cell Epigenetics of Tau Dementia"

Part 3 – Exploring Disease-enriched Glial States, Disease-Reactive Microglia and Astrocytes, and Genetic Heritability
bit.ly/4mZq6l7

#Epigenetics #Tauopathies #Chromatin #Dementia

Check out part 2 of 3 of our new blog on the "Single-cell Epigenetics of Tau Dementia"

Part 2 – "Exploring Disease-associated Dynamic Peaks, Functional Variants, eQTLs, and Cellular Subcluster Diversity"
bit.ly/47kwxKx

#Epigenetics #Tauopathies #Chromatin #Dementia

Check out part 1 of 3 of our new blog on the "Single-cell Epigenetics of Tau Dementia"

Part 1 – "Understanding Cell-specific CREs, Chromatin Accessibility, and Differentially-Accessible Regions in Tauopathies" bit.ly/47MFOLs

#Epigenetics #Tauopathies #Chromatin #Dementia

🧠 How to cure #tauopathies like #Alzheimers #Disease? First, we need to understand and model the causative #Tau accumulation in the #brain. @fichoulab.bsky.social and colleagues discuss challenges of #invitro #models in their latest Perspective.

➡️ doi.org/10.1002/1873-3468.70022

#neurobiology

Excited to be presenting our work on #Epigenomics of #Tauopathies and related diseases later this week at #Tau2025👇!

3-day #timelapse of #microscopy #live #imaging of neuron-glia cultures. Watch #astrocytes (highly motile) actively clearing deposited #Tau protein aggregates (fuzzy clusters). 🔍🧬 #Neuroscience #Tauopathies #Alzheimer

Figure describing and illustrating, through microscopy, the cellular culture model we used, the observation of aggregate internalization by glial cells, and the culture's stability under treatment. Full captions available in the link!

Figure describing the synaptic effects observed in neurons. It includes live imaging data over 3 days and 3D confocal microscopy images. Full captions available in the link!

Figure showing the results obtained on mitochondria in neurons and astrocytes. The use of a fluorescent and organelle-specific molecular probe provides insights into the oxidative state of mitochondria. Full captions available in the link!

🎉 First paper as 1st author!
We studied #astrocyte and #neuron responses to extracellular tau aggregates in #live #imaging: astrocyte #mitochondria adapt and influence #synapses! #neuroscience #tauopathies 🔬🧠
🔗 pubmed.ncbi.nlm.nih.gov/40122883/

#Timelapse de 3 jours d'imagerie en #microscopie #live de cultures neurones-glie. Observez les #astrocytes (très mobiles) nettoyant activement les agrégats de protéine #Tau déposés (amas diffus). 🔍🧬 #Neurosciences #Tauopathies #Alzheimer

Figure décrivant et illustrant par microscopie le modèle de culture cellulaire que nous avons utilisé, l'observation de l'internalisation des aggregats par des cellules gliales, et la stabilité de la culture face au traitement. Légendes complètes dans le lien!

Figure décrivant l'effet synaptique observé sur les neurones. On peut y voir des données d'imagerie sur les cultures vivantes (3 jours) et desacquisitions de microscpie confocale représentées 3 dimensions. Légendes complètes dans le lien!

Figure présentant les résultats obtenus sur les mitochondries des neurones et des astrocytes. L'utilisation d'une sonde moléculaire fluorescente et spécifique à ces organelles informe sur l'état oxydatif des mitochondries.

🎉Premier article en 1er auteur!🥳
Nous avons étudié la réaction d' #astrocytes et de #neurones aux agrégats de tau extracellulaires en #live #imaging: les #mitochondries astrocytaires s'adaptent et influencent les #synapses !
#neuroscience #tauopathies 🔬🧠
🔗 pubmed.ncbi.nlm.nih.gov/40122883/

In April, Angelika Dannert, #GSN graduate student from the lab working on a #iPSC model of #Tauopathies, graduated with flying colors. Big congrats Angelika (and thanks lab for the nice hat!)

These findings suggest that FTDP-17 with mutations in P301 should be considered
➡️ distinct inherited #tauopathies and that #model #systems with these mutations should be used with #caution in the study of #sporadic #tauopathies.