Rosmarinic Acid Inhibits Mitochondrial Damage by Alleviating Unfolded Protein Response

迷迭香酸通过减轻未折叠蛋白反应来抑制线粒体损伤

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作者:Guoen Cai ,Fabin Lin ,Dihang Wu ,Chenxin Lin ,Huiyun Chen ,Yicong Wei ,Huidan Weng ,Zhiting Chen ,Minxia Wu ,En Huang ,Zucheng Ye ,Qinyong Ye

Abstract

Mitochondria are essential organelles that perform important roles in cell biologies such as ATP synthesis, metabolic regulation, immunomodulatory, and apoptosis. Parkinson's disease (PD) is connected with mitochondrial neuronal damage related to mitochondrial unfolded protein response (mtUPR). Rosmarinic acid (RA) is a naturally occurring hydroxylated polyphenolic chemical found in the Boraginaceae and the Labiatae subfamily Nepetoideae. This study looked into RA's protective effect against mitochondrial loss in the substantia nigra (SN) caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the underlying mechanism associated with the mtUPR. Pretreatment with RA reduced motor impairments and dopaminergic neuronal degeneration in the SN of a mouse model injected with MPTP. Pretreatment of SH-SY5Y cells from cell viability loss, morphological damage, and oxidative stress. Furthermore, RA pre-injection suppressed MPTP-induced mtUPR, lowered the expression of HSPA9, HSPE1, CLPP, LONP1, and SIRT 4, and protected the MPTP-mice and SH-SY5Y cells from mitochondrial failure. These findings imply that RA can prevent Parkinson's disease by preventing mitochondrial damage in dopaminergic neurons in Parkinson's disease via alleviating mitochondrial unfolded protein response. Keywords: immunlogy; mitochondrial damage; mtUPR; rosmarinic acid; substantia nigra.

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