At @CBR_IISc, the Biomarker Centre of Excellence was inaugurated today, advancing research towards healthy brain aging. A new-gen biomarker analysis machine was launched by @kris_sg @niranjanbose @kvijayraghavan & Prof. Hari.

“Building a Collaborative Framework for Brain Aging” @CBR_IISc (Oct 27–28, Bangalore). Global & Indian experts unite on neurodegeneration research, biomarkers & therapies. #BrainAging #NeuroScience

Much needed 🚀 — India’s bold ₹1 Lakh Crore R&D push could be the inflection point for global science. The key will be sustained funding + translational focus across all sciences @movedisorder @ASAP_Research @mdsieditor

6/6- Pasca’s message: Human neuroscience has moved beyond just observing disease. We can now build circuits, test therapies, and model pathology in vitro & in vivo. Truly a keynote to remember. #mdscongress #Neuroscience @Sergiu_P_Pasca @movedisorder

5/6- 🚀 Applications span: Circuit & behavioral readouts Drug testing in human-like tissue Cell therapy transplantation into living animals Testing disease-modifying interventions in a human context

4/6- These models aren’t just “cool science.” They’re functional disease platforms: Timothy syndrome (CACNA1C) → drug development pipelines Epilepsy → seizure induction after assembloid transplantation Neurodevelopmental & psychiatric disorders

3/6-Unlike single organoids, assembloids mimic connectivity — cortical neurons projecting to striatum, interneuron migration, even multi-region loops firing in sync. 📊 Multi-region electrical recordings prove these circuits wire & fire like the real brain.

2/6- Pasca’s lab pioneered human iPSC-derived organoids & assembloids: 2D/3D neural cultures Region-specific organoids (cortex, striatum, cerebellum) “Assembloids” = linked brain regions wired together Even transplanted models for advanced maturation #mdscongress

Given the interest & request on more info on this talk, have added tweet thread (1/6)✨ Keynote by @Sergiu_P_Pasca was a masterclass in constructing & deconstructing the human brain Organoids to assembloids to in vivo transplantation — human neuroscience is entering a new era👇

🧠✨ At #MDSC9ngress, Sergiu Pasca showed how we can now build the brain in a dish — organoids & assembloids that wire, fire & even model seizures. Neuroscience is shifting from watching disease to constructing & testing the human nervous system. - translational @movedisorder

🧬 Just listened to “Decoding Parkinson’s genetics on a global scale” — a powerful reminder that long‑term, independent research infrastructure is what enables breakthroughs. 🎧 https://t.co/fMz81B6viV India needs similar long-term, research support. #TheGeneticsPodcast

This work is part of the GOPI-YOPD & PRAI initiatives. 💡 First report linking BSN mutations to specific motor symptoms in PD. 📄 Preprint live here ➡️ https://t.co/NQRFnSKHth @SingletonNeuro @huwmorris @cornelisblauw @movedisorder @MedGenomeLabs

👨‍🔬 Why it matters: Gait dysfunction in PD is poorly levodopa-responsive. If BSN is a key player, we may need to look beyond dopamine—toward synaptic scaffolds & protein aggregation control. 🧠 A new therapeutic target?

🛠️ Tools used: Variant prioritization: CADD, PolyPhen-2, AlphaMissense, I-Mutant2.0 Protein interaction networks: GeneMANIA + STRING Pathway analysis: Dopamine, ACh, GABA, serotonin pathways all implicated

🔥 Crossing Over: PD ↔ PSP BSN has been implicated in PSP-like syndromes Could BSN mutations drive tauopathy in some and synucleinopathy in others? A possible convergence node linking Parkinson’s and atypical parkinsonism

🧩 Mechanistic Clues BSN protein is vital for synaptic vesicle release—especially in dopaminergic & cholinergic neurons. Disruption here may affect gait control loops (e.g., PPN) → leading to FOG/postural instability Model organisms with BSN mutations show locomotor deficits too

🧠 Key Findings Patients with rare BSN mutations had: 2.6x ⬆️ odds for Freezing of Gait 2.3x ⬆️ odds for Shuffling C-terminal BSN mutations clustered in vesicle tethering domains 🧬 Suggests presynaptic dysfunction in motor control circuits

📌 Study Highlights 668 young-onset PD patients (South Asian cohort) Whole-exome sequencing: 110 BSN-positive cases 44 carried rare BSN mutations (MAF < 0.1%) Focus on motor symptoms: Freezing of Gait (FOG), Shuffling Gait (SG), Falls

🧠🧬 Can a synaptic scaffolding gene explain why some Parkinson’s freeze mid-step? New data from India 🇮🇳 suggests that Bassoon (BSN) mutations may be one of the missing link in PD gait dysfunction—and even PSP overlap. 👇 Dive in. #MDSCongress #Parkinsons #Genetics EPoster-1447

Does solving #proteinaggregation vs clearance hold the key to ageing disorders — maybe even an #elixir? Today’s #MDSCongress session on protein homeostasis was outstanding: 🔹 Lorraine – waste clearance 🔹 Kraus – aggregation in disease 🔹 Engelender – therapies @movedisorder