Blood-brain barrier-penetrative lipid nanoparticles enable systemic delivery of TRIM11 mRNA to disaggregate Tau in Alzheimer's disease models - PubMed
3 hours ago
- #Alzheimer's disease
- #Blood-brain barrier
- #mRNA therapy
- Hyperphosphorylated Tau aggregates are a key feature of Alzheimer's disease (AD), with no current approved therapy targeting them directly.
- TRIM11, an ATP-independent disaggregase, can dissolve pathological Tau fibrils and promote their clearance via the proteasome.
- A novel ligand-free lipid nanoparticle (PLNP) with PMPC enables blood-brain barrier (BBB) penetration by interacting with nAChRs and chTs.
- Systemic delivery of TRIM11 mRNA via PLNP results in significant hippocampal accumulation and neuronal transfection compared to unformulated mRNA.
- In 3×Tg-AD mice, PLNP-mTRIM11 reduces Tau aggregates, decreases neuroinflammation, restores neuronal integrity, and improves cognitive functions for at least 3 months.
- Early prophylactic treatment with PLNP-mTRIM11 prevents Tau pathology and maintains cognitive function, suggesting its potential for tauopathy therapy.