Background pattern of a brain with neural connections

Team Doxakis

Decoding co-pathological mechanisms in Parkinson’s disease: from molecular interactions to disease progression

2026-Present

Parkinson’s disease exhibits substantial clinical heterogeneity driven in part by co-aggregation of α synuclein, tau, and TDP43 proteins. This proposal investigates how chronic cellular stress reduces membraneless organelle fluidity through altered liquid-liquid phase separation, trapping RNA-binding proteins and disrupting transcription, splicing, and proteostasis. These perturbations create synergistic protein aggregation that accelerates neurodegeneration along vulnerable midbrain-cortical circuits. Using iPSC-derived midbrain assembloids, transgenic rats, and stratified human brain samples, the study will define molecular mechanisms underlying co-pathology formation, identify quantitative signatures predicting disease progression, and validate therapeutic targets for treating PD heterogeneity.

Tags
AggregationAlpha-synucleinAnimal modelsGBA (Glucocerebrosidase)Liquid-liquid phase separationLRRK2Multi-omicsNeurodegenerationOrganoidPathomechanismSingle-cell multi-omicsSingle-cell transcriptomics

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In the News

Decoding the Blueprint: Advancing Personalized Parkinson’s Treatments

Decoding the Blueprint: Advancing Personalized Parkinson’s Treatments

05/21/2026 — In our community, we often hear: “If you’ve met one person with Parkinson’s, you’ve met one person with Parkinson’s.” This isn’t just an adage — it’s a biological reality. This radical variability is exactly what makes the disease so difficult to outsmart. We’ve learned that a puzzle this fragmented cannot be solved with a single, broad stroke. Our goal isn’t to find one answer for everyone, but the right answer for the right person at the right time.

Aligning Science Across Parkinson’s and The Michael J. Fox Foundation Expand Global Research Initiative with $261M Investment Toward Personalized Treatments

Aligning Science Across Parkinson’s and The Michael J. Fox Foundation Expand Global Research Initiative with $261M Investment Toward Personalized Treatments

04/28/2026 — Today, Aligning Science Across Parkinson’s (ASAP), in partnership with The Michael J. Fox Foundation for Parkinson’s Research (MJFF), announced $261 million in new grant funding for the Collaborative Research Network (CRN) to map the biological blueprint of Parkinson’s disease and build a standardized toolkit of global research resources that are needed to turn discoveries into treatments.

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Members of the CRN work diligently to advance our understanding of Parkinson’s disease. Learn more about recent CRN discoveries and achievements.