首页|Targeting modulation of intestinal flora through oral route by an antimicrobial nucleic acid-loaded exosome-like nanovesicles to improve Parkinson's disease

Targeting modulation of intestinal flora through oral route by an antimicrobial nucleic acid-loaded exosome-like nanovesicles to improve Parkinson's disease

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Targeting modulation of intestinal flora through oral route by an antimicrobial nucleic acid-loaded exosome-like nanovesicles to improve Parkinson's disease
Parkinson's disease(PD)is one of the most prevalent neurodegenerative diseases.It is usually accompa-nied by motor and non-motor symptoms that seriously threaten the health and the quality of life.Novel medications are urgently needed because current pharmaceuticals can relieve symptoms but cannot stop disease progression.The microbiota-gut-brain axis(MGBA)is closely associated with the occurrence and development of PD and is an effective therapeutic target.Tetrahedral framework nucleic acids(tFNAs)can modulate the microbiome and immune regulation.However,such nucleic acid nanostructures are very sensitive to acids which hinder this promising approach.Therefore,we prepared exosome-like nanovesicles(Exo@tac)from ginger that are acid resistant and equipped with tFNAs modified by antimi-crobial peptides(AMP).We verified that Exo@tac regulates intestinal bacteria associated with the microbial-gut-brain axis in vitro and significantly improves PD symptoms in vivo when administered orally.Microbiota profiling confirmed that Exo@tac normalizes the intestinal flora composition of mouse models of PD.Our findings present a novel strategy for the development of PD drugs and the innovative delivery of nucleic acid nanomedicines.

Parkinson's diseaseTetrahedral framework nucleic acidsMicrobial-gut-brain axisExosome-like nanovesiclesIntestinal flora

Weitong Cui、Zhiyong Guo、Xingyu Chen、Ran Yan、Wenjuan Ma、Xiao Yang、Yunfeng Lin

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State Key Laboratory of Oral Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu 610041,China

Psychiatric Laboratory and Mental Health Center,the State Key Laboratory of Biotherapy,West China Hospital of Sichuan University,Chengdu 610041,China

Parkinson's disease Tetrahedral framework nucleic acids Microbial-gut-brain axis Exosome-like nanovesicles Intestinal flora

2024

10.1016/j.scib.2024.10.027

科学通报(英文版)
中国科学院

科学通报(英文版)

CSTPCD
ISSN：1001-6538
年,卷(期)：2024.69(24)