Inhibition of α-synuclein aggregation by MT101-5 is neuroprotective in mouse models of Parkinson’s disease

• Published in: Biomedicine & pharmacotherapy Vol. 154; p. 113637
• Main Authors: Kim, Sinyeon, Choi, Jin Gyu, Kim, Se Woong, Park, Sang Cheol, Kang, Yu-ra, Park, Dong Seok, Son, Miwon, Lee, Choong Hwan
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01.10.2022; Elsevier
• Subjects: Chaperone; Mitochondria; MT101-5; Parkinson’s disease; Proteasome; α-Synuclein aggregation; ST; Chaperone; α-Synuclein aggregation; SNpc; α-syn PFF; GR; MPP; MT101-5; PCA; CR; Mitochondria; PD; α-syn; ROS; MOA; Parkinson’s disease; GF; Proteasome
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2022.113637

Parkinson's disease (PD) is the second most common neurodegenerative disease, after Alzheimer's disease, and becomes increasingly prevalent with age. α-Synuclein (α-syn) forms the major filamentous component of Lewy bodies, which are pathological hallmarks of α-synucleinopathies such as PD. We evaluated the neuroprotective effects of MT101-5, a standardized herbal formula that consists of an ethanolic extract of Genkwae Flos, Clematidis Radix, and Gastrodiae Rhizoma, against α-synuclein-induced cytotoxicity in vivo. MT101-5 protected against behavioral deficits and loss of dopaminergic neurons in human α-syn-overexpressing transgenic mice after treatment with 30 mg/kg/day for 5 months. We investigated transcriptomic changes within MT101-5 mechanisms of action (MOA) suppressing α-syn aggregation in an α-synuclein preformed fibril (α-syn PFF) mouse model of sporadic PD. We found that inhibition of α-syn fibril formation was associated with changes in transcripts in mitochondrial biogenesis, electron transport, chaperones, and proteasomes following treatment with MT101-5. These results suggest that the mixed herbal formula MT101-5 may be used as a pharmaceutical agent for preventing or improving PD. [Display omitted] •MT101-5 treatment improves α-synuclein aggregation-induced motor dysfunctions.•MT101-5 treatment reduces the accumulation of α-synuclein fibril-induced damage in dopaminergic neurons.•MT101-5 MoA demonstrates activation of chaperone and proteasome, mitochondrial biosynthesis, oxidative phosphorylation (ATP production) by RNA sequencing-based transcriptome analysis.•MT101-5 validates the enhancement of mitochondrial ATP generation and inhibition of programmed cell death in SH-SY5Y cells under MPP+-induced oxidative stress and apoptosis.