Treating LRRK2‐Related Parkinson's Disease by Inhibiting the mTOR Signaling Pathway to Restore Autophagy

Parkinson's disease (PD) is the most common chronic neurodegenerative disease and is characterized by motor dysfunctions. Pathogenic mutations in leucine‐rich repeat kinase 2 (LRRK2) are a major cause of the neurotoxicity that causes PD. As an inhibitor of LRRK2 activity, vitamin B12 (VB12) is...

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Bibliographic Details
Published in:Advanced functional materials 2021-09, Vol.31 (38), p.n/a
Main Authors: Cui, Weitong, Yang, Xiao, Chen, Xingyu, Xiao, Dexuan, Zhu, Junyao, Zhang, Mei, Qin, Xin, Ma, Xiaohong, Lin, Yunfeng
Format: Article
Language:English
Subjects:
Autophagy
Kinases
Leucine
leucine‐rich repeat kinase 2
Materials science
Mutation
Nucleic acids
Parkinson's disease
Signs and symptoms
tetrahedral framework nucleic acid
vitamin B12
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Summary:Parkinson's disease (PD) is the most common chronic neurodegenerative disease and is characterized by motor dysfunctions. Pathogenic mutations in leucine‐rich repeat kinase 2 (LRRK2) are a major cause of the neurotoxicity that causes PD. As an inhibitor of LRRK2 activity, vitamin B12 (VB12) is a promising therapeutic option for PD and is shown to restore autophagy in PD models. However, the dependence on transporters and the extremely low brain tissue utilization of VB12 limit its therapeutic effects. Based on this, VB12‐loaded tetrahedral framework nucleic acid (TVC) is synthesized and its effectiveness in the model of PD induced with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine is evaluated. TVC provides better recovery of autophagy than free VB12 did both in vivo and in vitro, leading to enhanced clearing of abnormal protein accumulations and restoration of PD motor symptoms. It is believed that TVC has broad therapeutic potential in the treatment of PD and similar neurodegenerative diseases. Vitamin B12 (VB12) is loaded into the tetrahedral framework nucleic acid (TFNA) to synthesize TFNA‐VB12 complex (TVC) through electrostatic interaction, and the effectiveness of TVC in Parkinson's disease (PD) is evaluated. TVC provides better brain tissue distribution and autophagy recovery than VB12, leading to the removal of abnormal protein accumulation and the recovery of PD motor symptoms.
ISSN:1616-301X
1616-3028
DOI:10.1002/adfm.202105152