A microfluidic approach to rescue ALS motor neuron degeneration using rapamycin

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 immunosuppr...

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Autores principales:	Phaneendra Chennampally, Ambreen Sayed-Zahid, Prabakaran Soundararajan, Jocelyn Sharp, Gregory A. Cox, Scott D. Collins, Rosemary L. Smith
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/23565040243649bfa7f93f608d89949b
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spelling	oai:doaj.org-article:23565040243649bfa7f93f608d89949b2021-12-02T17:23:39ZA microfluidic approach to rescue ALS motor neuron degeneration using rapamycin10.1038/s41598-021-97405-12045-2322https://doaj.org/article/23565040243649bfa7f93f608d89949b2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97405-1https://doaj.org/toc/2045-2322Abstract 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.Phaneendra ChennampallyAmbreen Sayed-ZahidPrabakaran SoundararajanJocelyn SharpGregory A. CoxScott D. CollinsRosemary L. SmithNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Phaneendra Chennampally Ambreen Sayed-Zahid Prabakaran Soundararajan Jocelyn Sharp Gregory A. Cox Scott D. Collins Rosemary L. Smith A microfluidic approach to rescue ALS motor neuron degeneration using rapamycin
description	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.
format	article
author	Phaneendra Chennampally Ambreen Sayed-Zahid Prabakaran Soundararajan Jocelyn Sharp Gregory A. Cox Scott D. Collins Rosemary L. Smith
author_facet	Phaneendra Chennampally Ambreen Sayed-Zahid Prabakaran Soundararajan Jocelyn Sharp Gregory A. Cox Scott D. Collins Rosemary L. Smith
author_sort	Phaneendra Chennampally
title	A microfluidic approach to rescue ALS motor neuron degeneration using rapamycin
title_short	A microfluidic approach to rescue ALS motor neuron degeneration using rapamycin
title_full	A microfluidic approach to rescue ALS motor neuron degeneration using rapamycin
title_fullStr	A microfluidic approach to rescue ALS motor neuron degeneration using rapamycin
title_full_unstemmed	A microfluidic approach to rescue ALS motor neuron degeneration using rapamycin
title_sort	microfluidic approach to rescue als motor neuron degeneration using rapamycin
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/23565040243649bfa7f93f608d89949b
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A microfluidic approach to rescue ALS motor neuron degeneration using rapamycin

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