iPS cells-derived exosomes - impact on mitochondrial (dys)function in Huntington's disease and potential nanodelivery system for microRNA-based therapeutics

Overview

Project Summary

The present project aims to determine the mechanism involved in the pathogenic propagation of Huntington's disease(HD)-related proteins and nucleotides and develop novel exosome nanotechnology for the treatment of mitochondrial dysfunction in HD. HD is a monogenic neurodegenerative disorder caused by a mutation in the huntingtin gene. Several mechanisms have been linked to disease progression but recently the propagation hypothesis has gained relevance. Exosomes naturally transport RNA/DNA and proteins between cells and can underlie a pathway for pathology spreading. By using human fibroblasts from HD patients and derived induced pluripotent stem cells and striatal-like neurons we intent to unravel the role of proteomic, mitochondrial DNA and microRNA exosomal content in HD neuropathology. Moreover, taking advantage of exosomes as nanocarriers we propose to identify an exosomal microRNA that may rescue HD-induced mitochondrial dysfunction and thus promote survival.

Main Goals

This study is expected to determine the mechanism involved in the pathogenic propagation of Huntington's disease(HD)-related proteins and identify specific exosomal micro(mi)RNA that may rescue HD-induced mitochondrial dysfunction and striatal synaptic dysfunction.

Project Details