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Cell-Permeable HSP70 Protects Neurons and Astrocytes Against Cell Death in the Rotenone-Induced and Familial Models of Parkinson’s Disease

Vinokurov, Andrey Y; Palalov, Alexander A; Kritskaya, Kristina A; Demyanenko, Svetlana V; Garbuz, David G; Evgen'ev, Michael B; Esteras, Noemi; (2024) Cell-Permeable HSP70 Protects Neurons and Astrocytes Against Cell Death in the Rotenone-Induced and Familial Models of Parkinson’s Disease. Molecular Neurobiology 10.1007/s12035-024-04077-9. (In press). Green open access

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Abstract

Heat shock protein 70 (HSP70) is activated under stress response. Its involvement in cell protection, including energy metabolism and quality control makes it a promising pharmacological target. A strategy to increase HSP70 levels inside the cells is the application of recombinant HSP70. However, cell permeability and functionality of these exogenously applied proteins inside the cells is still disputable. Here, using fluorescence- labeled HSP70, we have studied permeability and distribution of HSP70 inside primary neurons and astrocytes, and how exogenous HSP70 changes mitochondrial metabolism and mitophagy. We have found that exogenous recombinant HSP70 can penetrate the neurons and astrocytes and distributes in mitochondria, lysosomes and in lesser degree in the endoplasmic reticulum. HSP70 increases mitochondrial membrane potential in control neurons and astrocytes, and in fibroblasts of patients with familial Parkinson´s disease (PD) with PINK1 and LRRK2 mutations. Increased mitochondrial membrane potential was associated with higher mitochondrial ROS production and activation of mitophagy. Importantly, preincubation of the cells with HSP70 protected neurons and astrocytes against cell death in a toxic model of PD induced by rotenone, and in the PINK1 and LRRK2 PD human fibroblasts. Thus, exogenous recombinant HSP70 is cell permeable, and acts as endogenous HSP70 protecting cells in the case of toxic model and familial forms of Parkinson’s Disease.

Type: Article
Title: Cell-Permeable HSP70 Protects Neurons and Astrocytes Against Cell Death in the Rotenone-Induced and Familial Models of Parkinson’s Disease
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s12035-024-04077-9
Publisher version: http://dx.doi.org/10.1007/s12035-024-04077-9
Language: English
Additional information: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Hsp70; Mitophagy; Mitochondria; Lysosomes; Parkinson’s Disease
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10188616
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