P 5 MCC950 treatment reduces neuroinflammation, rescues neuronal cell death and ameliorates motor deficits in the AAV1/2-A53T-αSyn mouse model of Parkinson's disease

Grotemeyer, Alexander; Fischer, Jonas; Koprich, James B.; Brotchie, Jonathan M.; Volkmann, Joh.; Ip, Chi Wang

doi:10.1016/j.clinph.2022.01.036

Cited by 1 publication

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“…[16,17] In neurodegenerative conditions, the persistent aggregation of misfolded protein can activate the NLRP3 inflammasome, exacerbating central nervous system (CNS) inflammation and neuropathology, and forming a bidirectional pathogenic cycle. [18][19][20][21] Especially, a recent study has systematically explored the pathological mechanism in postmortem PD brains and in various PD rodent models, and found that ROS and mitochondrial dysfunction have inextricable connections with NLRP3 inflammasome activation. [22] These findings indicate that the activation of NLRP3 inflammasome by ROS acts as a primary executor of neuroinflammation and a key interactive communication site in PD pathology, highlighting NLRP3 as a promising target for PD treatment.…”

Section: Introductionmentioning

confidence: 99%

Metal–Organic Framework Based Nanozyme System for NLRP3 Inflammasome‐Mediated Neuroinflammatory Regulation in Parkinson's Disease

Li,

Ding,

Chang

et al. 2023

Adv Healthcare Materials

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Neuroinflammation is associated with a series of pathological symptoms in Parkinson's disease (PD), including α‐synuclein aggregation and dopaminergic neuronal death. The NOD‐like receptor protein 3 (NLRP3) inflammasome plays a crucial role in neuroinflammation at the lesion site and is a promising target for PD treatment. In this study, a nanoscale metal‐organic framework (Zr‐FeP MOF) based nanozyme is fabricated using Fe‐5,10,15,20‐tetra (4‐carboxyphenyl) porphyrin (Fe‐TCPP) and Zr6 cluster as ligands. The Zr‐FeP MOF is subsequently encapsulated with mannitol (Man)‐liposome, resulting in the formation of Zr‐FeP MOF@Man liposome (MOF@Man Liposome) nanozyme system. The in vitro studies show that this nanozyme system is effective in relieving the formation of NLRP3 inflammasome and mitochondrial dysfunction. In mouse models of PD, the nanozyme system demonstrates a significant blood–brain barrier‐crossing capability attributed to the Man‐mediated brain targeting. Additionally, transcriptomic and biochemical studies show that the nanozyme system effectively inhibits the formation and assembly of inflammasome components, mitigating the activation of glial cells and neuroinflammatory response, and ultimately regulating the pathological symptoms of PD effectively.

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