Receptor tyrosine kinase ROR1 ameliorates Aβ1–42 induced cytoskeletal instability and is regulated by the miR146a-NEAT1 nexus in Alzheimer’s disease

Abstract Alzheimer’s disease (AD) involves severe cytoskeletal degradation and microtubule disruption. Here, we studied the altered dynamics of ROR1, a Receptor Tyrosine Kinase (RTK), and how it could counter these abnormalities. We found that in an Aβ1–42 treated cell model of AD, ROR1 was signific...

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Autores principales:	Kaushik Chanda, Nihar Ranjan Jana, Debashis Mukhopadhyay
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/27441665e72147fd9531494c4e41b8af
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spelling	oai:doaj.org-article:27441665e72147fd9531494c4e41b8af2021-12-02T17:37:12ZReceptor tyrosine kinase ROR1 ameliorates Aβ1–42 induced cytoskeletal instability and is regulated by the miR146a-NEAT1 nexus in Alzheimer’s disease10.1038/s41598-021-98882-02045-2322https://doaj.org/article/27441665e72147fd9531494c4e41b8af2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98882-0https://doaj.org/toc/2045-2322Abstract Alzheimer’s disease (AD) involves severe cytoskeletal degradation and microtubule disruption. Here, we studied the altered dynamics of ROR1, a Receptor Tyrosine Kinase (RTK), and how it could counter these abnormalities. We found that in an Aβ1–42 treated cell model of AD, ROR1 was significantly decreased. Over expressed ROR1 led to the abrogation of cytoskeletal protein degradation, even in the presence of Aβ1–42, preserved the actin network, altered actin dynamics and promoted neuritogenesis. Bioinformatically predicted miRNAs hsa-miR-146a and 34a were strongly up regulated in the cell model and their over expression repressed ROR1. LncRNA NEAT1, an interactor of these miRNAs, was elevated in mice AD brain and cell model concordantly. RNA Immunoprecipitation confirmed a physical interaction between the miRNAs and NEAT1. Intuitively, a transient knock down of NEAT1 increased their levels. To our knowledge, this is the first instance which implicates ROR1 in AD and proposes its role in preserving the cytoskeleton. The signalling modalities are uniquely analyzed from the regulatory perspectives with miR-146a and miR-34a repressing ROR1 and in turn getting regulated by NEAT1.Kaushik ChandaNihar Ranjan JanaDebashis MukhopadhyayNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kaushik Chanda Nihar Ranjan Jana Debashis Mukhopadhyay Receptor tyrosine kinase ROR1 ameliorates Aβ1–42 induced cytoskeletal instability and is regulated by the miR146a-NEAT1 nexus in Alzheimer’s disease
description	Abstract Alzheimer’s disease (AD) involves severe cytoskeletal degradation and microtubule disruption. Here, we studied the altered dynamics of ROR1, a Receptor Tyrosine Kinase (RTK), and how it could counter these abnormalities. We found that in an Aβ1–42 treated cell model of AD, ROR1 was significantly decreased. Over expressed ROR1 led to the abrogation of cytoskeletal protein degradation, even in the presence of Aβ1–42, preserved the actin network, altered actin dynamics and promoted neuritogenesis. Bioinformatically predicted miRNAs hsa-miR-146a and 34a were strongly up regulated in the cell model and their over expression repressed ROR1. LncRNA NEAT1, an interactor of these miRNAs, was elevated in mice AD brain and cell model concordantly. RNA Immunoprecipitation confirmed a physical interaction between the miRNAs and NEAT1. Intuitively, a transient knock down of NEAT1 increased their levels. To our knowledge, this is the first instance which implicates ROR1 in AD and proposes its role in preserving the cytoskeleton. The signalling modalities are uniquely analyzed from the regulatory perspectives with miR-146a and miR-34a repressing ROR1 and in turn getting regulated by NEAT1.
format	article
author	Kaushik Chanda Nihar Ranjan Jana Debashis Mukhopadhyay
author_facet	Kaushik Chanda Nihar Ranjan Jana Debashis Mukhopadhyay
author_sort	Kaushik Chanda
title	Receptor tyrosine kinase ROR1 ameliorates Aβ1–42 induced cytoskeletal instability and is regulated by the miR146a-NEAT1 nexus in Alzheimer’s disease
title_short	Receptor tyrosine kinase ROR1 ameliorates Aβ1–42 induced cytoskeletal instability and is regulated by the miR146a-NEAT1 nexus in Alzheimer’s disease
title_full	Receptor tyrosine kinase ROR1 ameliorates Aβ1–42 induced cytoskeletal instability and is regulated by the miR146a-NEAT1 nexus in Alzheimer’s disease
title_fullStr	Receptor tyrosine kinase ROR1 ameliorates Aβ1–42 induced cytoskeletal instability and is regulated by the miR146a-NEAT1 nexus in Alzheimer’s disease
title_full_unstemmed	Receptor tyrosine kinase ROR1 ameliorates Aβ1–42 induced cytoskeletal instability and is regulated by the miR146a-NEAT1 nexus in Alzheimer’s disease
title_sort	receptor tyrosine kinase ror1 ameliorates aβ1–42 induced cytoskeletal instability and is regulated by the mir146a-neat1 nexus in alzheimer’s disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/27441665e72147fd9531494c4e41b8af
work_keys_str_mv	AT kaushikchanda receptortyrosinekinaseror1amelioratesab142inducedcytoskeletalinstabilityandisregulatedbythemir146aneat1nexusinalzheimersdisease AT niharranjanjana receptortyrosinekinaseror1amelioratesab142inducedcytoskeletalinstabilityandisregulatedbythemir146aneat1nexusinalzheimersdisease AT debashismukhopadhyay receptortyrosinekinaseror1amelioratesab142inducedcytoskeletalinstabilityandisregulatedbythemir146aneat1nexusinalzheimersdisease
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Receptor tyrosine kinase ROR1 ameliorates Aβ1–42 induced cytoskeletal instability and is regulated by the miR146a-NEAT1 nexus in Alzheimer’s disease

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