Nuclear material transfer in pathogenic protein spreading

Principal Investigator

Project Goals

Spreading of pathogenic protein aggregates in neurons causes progression of Alzheimer’s disease and many genetic and age-related neurological disorders. This project will investigate a previously unrecognized population of Sox-10 lineage cells that transfer nuclear and ribosomal material to neurons and their role in pathogenic protein spreading. Our research will advance our understanding of the mechanisms underlying pathogenic protein spreading with the aim to develop novel therapies to treat Alzheimer’s disease and other devastating disorders of the nervous system.

Project Summary

In Aim 1, we will use RNA-seq to determine molecular profiles of Sox10-lineage oligodendroglia (SOL) that transfer nuclear material to neurons and identify common characteristics of receiving neurons. We will identify signaling pathways engaged in SOL-neuron interaction and transcriptional changes in response to neuroinflammation. In Aim 2, we will examine the role of SOL in pathogenic protein spreading. We will use transgenic mice with controlled overexpression of mutant TDP-43 in SOL to evaluate the effects on brain pathology and behavior in relation to Alzheimer’s disease.

Publications

First published on: April 23, 2024

Last modified on: July 22, 2024