Beta Amyloid Peptide: Research Paper : Haploinsufficiency of the TDP43 ubiquitin E3 ligase RNF220 leads to ALS-like motor neuron defects in the mouse

Haploinsufficiency of the TDP43 ubiquitin E3 ligase RNF220 leads to ALS-like motor neuron defects in the mouse

Abstract

TDP43 pathology is seen in a large majority of amyotrophic lateral sclerosis (ALS) cases, suggesting a central pathogenic role of this regulatory protein. Clarifying the molecular mechanism controlling TDP43 stability and subcellular location might provide important insights into ALS therapy. The ubiquitin E3 ligase RNF220 is involved in different neural developmental processes through various molecular targets in the mouse. Here, we report that the RNF220+/- mice showed progressively decreasing mobility to different extents, some of which developed typical ALS pathological characteristics in spinal motor neurons, including TDP43 cytoplasmic accumulation, atrocytosis, muscle denervation, and atrophy. Mechanistically, RNF220 interacts with TDP43 in vitro and in vivo and promotes its polyubiquitination and proteasomal degradation. In conclusion, we propose that RNF220 might be a modifier of TDP43 function in vivo and contribute to TDP43 pathology in neurodegenerative disease like ALS.

Keywords: RNF220; TDP43; amyotrophic lateral sclerosis (ALS); polyubiquitination.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33369790/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.