Kang 2018 Exp Mol Med
|Kang YC, Son M, Kang S, Im S, Piao Y, Lim KS, Song MY, Park KS, Kim YH, Pak YK (2018) Cell-penetrating artificial mitochondria-targeting peptide-conjugated metallothionein 1A alleviates mitochondrial damage in Parkinson's disease models. Exp Mol Med 50:105.|
Abstract: An excess of reactive oxygen species (ROS) relative to the antioxidant capacity causes oxidative stress, which plays a role in the development of Parkinson's disease (PD). Because mitochondria are both sites of ROS generation and targets of ROS damage, the delivery of antioxidants to mitochondria might prevent or alleviate PD. To transduce the antioxidant protein human metallothionein 1A (hMT1A) into mitochondria, we computationally designed a cell-penetrating artificial mitochondria-targeting peptide (CAMP). The recombinant CAMP-conjugated hMT1A fusion protein (CAMP-hMT1A) successfully localized to the mitochondria. Treating a cell culture model of PD with CAMP-hMT1A restored tyrosine hydroxylase expression and mitochondrial activity and reduced ROS production. Furthermore, injection of CAMP-hMT1A into the brain of a mouse model of PD rescued movement impairment and dopaminergic neuronal degeneration. CAMP-hMT1A delivery into mitochondria might be therapeutic against PD by alleviating mitochondrial damage, and we predict that CAMP could be used to deliver other cargo proteins to the mitochondria.
Labels: MiParea: Respiration, mt-Medicine, Pharmacology;toxicology Pathology: Parkinson's
Organism: Human Tissue;cell: Nervous system Preparation: Isolated mitochondria
Coupling state: OXPHOS Pathway: N HRR: Oxygraph-2k