Document Type

Article

Publication Date

9-13-2021

Publication Title

Sci Rep

Keywords

JMG

JAX Source

Sci Rep 2021 Sep 13; 11(1):18168

Volume

11

Issue

1

First Page

18168

Last Page

18168

ISSN

2045-2322

PMID

34518579

DOI

https://doi.org/10.1038/s41598-021-97405-1

Abstract

TAR DNA-binding protein-43 (TDP-43) is known to accumulate in ubiquitinated inclusions of amyotrophic lateral sclerosis affected motor neurons, resulting in motor neuron degeneration, loss of motor functions, and eventually death. Rapamycin, an mTOR inhibitor and a commonly used immunosuppressive drug, has been shown to increase the survivability of Amyotrophic Lateral Sclerosis (ALS) affected motor neurons. Here we present a transgenic, TDP-43-A315T, mouse model expressing an ALS phenotype and demonstrate the presence of ubiquitinated cytoplasmic TDP-43 aggregates with > 80% cell death by 28 days post differentiation in vitro. Embryonic stem cells from this mouse model were used to study the onset, progression, and therapeutic remediation of TDP-43 aggregates using a novel microfluidic rapamycin concentration gradient generator. Results using a microfluidic device show that ALS affected motor neuron survival can be increased by 40.44% in a rapamycin dosage range between 0.4-1.0 µM.

Comments

This article is licensed under a Creative Commons Attribution 4.0 International License.

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