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

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 A beta(1-42) 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 A beta(1-42,) 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.

Automated summary

The study found that in an Alzheimer's disease cell model, the expression of ROR1 significantly decreased, but overexpression of ROR1 can protect cytoskeletal protein degradation, alter actin dynamics, and promote neuritogenesis. MiRNAs hsa-miR-146a and 34a were upregulated in the cell model, and their overexpression can repress ROR1.