iiinova — where your digital self keeps evolving

Xiaobo Mao @xiaobomao.bsky.social · 19/10/2025

Great collaboration with Jingxin Wang, Mingyao Ying, @TedDawson_Lab, @LianaRosenthal & our amazing teams. Kudos to first author Ning Wang! #Parkinsons #LBD #RNAtherapeutics #neuroscience @HopkinsMedicine

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Xiaobo Mao @xiaobomao.bsky.social · 19/10/2025

New @bioRxiv: We built PMO-based RNA-degrading chimeras (RDCs) to degrade SNCA mRNA & lower α-synuclein. This approach prevents prion-like seeding & protects neurons in cellular & *in vivo* models. A promising new therapy for #synucleinopathies. doi.org/10.1101/2025...

doi.org

Targeted α-Synuclein mRNA Degradation by PMO-Based RNA-Degrading Chimeras

α-Synucleinopathies are devastating neurodegenerative diseases characterized by pathological accumulation of a neuronal protein, α-synuclein (αSyn). Lowering soluble αSyn levels is a promising therape...

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Xiaobo Mao @xiaobomao.bsky.social · 08/09/2025

This was a massive team effort! Huge thanks to all authors, collaborators, institutions, and funders. Read the full paper here: www.science.org/doi/10.1126/...

science.org

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Xiaobo Mao @xiaobomao.bsky.social · 08/09/2025

Why this matters: We've identified a key environmental trigger for LBD pathogenesis. This specific, pollution-induced α-synuclein strain is a novel target for developing future treatments and prevention strategies. #publichealth #environment

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Xiaobo Mao @xiaobomao.bsky.social · 08/09/2025

Confirmed in mouse models: the 'PM-PFF' strain caused cognitive deficits. Critically, mice genetically lacking the α-synuclein protein were protected from PM₂.₅-induced brain damage and cognitive decline, proving the protein's central role.

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Xiaobo Mao @xiaobomao.bsky.social · 08/09/2025

The mechanism? PM₂.₅ exposure creates a unique, highly toxic α-synuclein strain we named 'PM-PFF'. This new strain is more aggressive and neurotoxic, closely mimicking the pathogenic protein aggregates found in human LBD brains. #research #neurology

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Xiaobo Mao @xiaobomao.bsky.social · 08/09/2025

Our new study in @sciencemagazine.bsky.social finds a direct link: air pollution (PM₂.₅) and Lewy body dementia (LBD). Analyzing data from 56M+ people, we show chronic PM₂.₅ exposure significantly increases LBD risk. #neuroscience #dementia #LBD

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Xiaobo Mao @xiaobomao.bsky.social · 17/08/2025

Join the Mao Lab @ Johns Hopkins to study Parkinson’s & Alzheimer. Work with a PI w/ 100+ publications (incl. recent Science) Strong career mentorship Collaborative environment Apply: xmao4@jhmi.edu #Postdoc #Neuroscience #AcademicJobs #JohnsHopkins #Neurodegeneration #Research

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Xiaobo Mao @xiaobomao.bsky.social · 12/07/2025

5/5 Our work uncovers a potent RNS-driven pathway, offers a mechanistic link for neurotoxicity associated with environmental copper pollution, and provides a critical design principle for neuroprotective nanozymes. Check out our preprint on bioRxiv! www.biorxiv.org/content/10.1...

biorxiv.org

Copper-containing ROS-scavenging nanozyme paradoxically drives α-synucleinopathy by amplifying nitrosative stress

Reactive oxygen and nitrogen species (RONS) are implicated in neurodegeneration, but their specific pathogenic roles remain unclear. Here, we developed a pair of iridium-based nanozymes with opposing ...

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Xiaobo Mao @xiaobomao.bsky.social · 12/07/2025

4/5 The efficacy of the Ir nanozyme isn't limited to one scenario. We showed it works across three diverse and clinically relevant models: a brain-first model, a body-first (gut-to-brain) model, and a complex AD/PD co-pathology model. #DrugDiscovery

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Xiaobo Mao @xiaobomao.bsky.social · 12/07/2025

3/5 This new mechanistic insight allowed us to validate a powerful therapeutic strategy. A copper-free, broad-spectrum RONS-scavenging iridium (Ir) nanozyme demonstrated substantial therapeutic efficacy, rescuing pathology and restoring function. #Nanomedicine #Parkinsons

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Xiaobo Mao @xiaobomao.bsky.social · 12/07/2025

2/5 The paradox is resolved: Our copper-doped nanozyme (Ir₃Cu), while scavenging ROS, uniquely amplifies reactive nitrogen species (RNS). This revealed the potent, independent pathogenic potential of RNS in driving α-synuclein propagation, a finding confirmed by pharmacology & transcriptomics.

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Xiaobo Mao @xiaobomao.bsky.social · 12/07/2025

1/5 Can an “antioxidant” nanozyme make neurodegeneration worse? 🤯 In our new work, we designed a potent ROS-scavenging nanozyme. It paradoxically exacerbated Parkinson's-like pathology. This surprising result led to a major discovery. #Neuroscience #Nanozyme

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