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

Abstract

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-1,2,3,6tetrahydropyridine 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.

Tetrahedral framework nucleic acids-based delivery of microRNA-155 inhibits choroidal neovascularization by regulating the polarization of macrophages

“…In terms of drug or gene delivery, tetrahedral framework nucleic acids (tFNAs) are a promising vector. The tFNAs are a three-dimensional structure synthesized from four pieces of single strand DNA [ [23] , [24] , [25] ]. Due to the source of its components, its good biosafety and biocompatibility have been proven in previous studies [ [26] , [27] , [28] ].…”

Treatment effect of DNA framework nucleic acids on diffuse microvascular endothelial cell injury after subarachnoid hemorrhage

“… 14 Furthermore, abundant evidence has confirmed that tFNAs successfully alleviate apoptosis of various cell types by restoring normal nuclear morphology, reversing cell cycle abnormalities, and affecting apoptosis mediators. 12 , 15 , 16 …”

Application of Programmable Tetrahedral Framework Nucleic Acid-Based Nanomaterials in Neurological Disorders: Progress and Prospects

“…Another study reported that through electrostatic incubation, the tFNA could successfully transport therapeutic VB12 across the BBB in the treatment of PD (Cui et al, 2021). VB12 is a potential therapy for PD that has been shown to promote autophagy in PD models.…”