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Protein misfolding and aggregation is thought to be one of the initial events leading to neurodegenerative changes in a variety of brain diseases, including amyotrophic lateral sclerosis (ALS), frontal lobe dementia, Parkinson's disease, Alzheimer's disease, and Huntington's disease (HD), collectively known as protein misfolding disorder (PMDs).
neuron protein steady state is a prominent feature of many neurodegenerative diseases, mainly manifested in the change of endodernet (ER) function.
the team of authors has previously reported on the target transcription factor XBP1, a key medium for endoensurgen stress response, which slows disease progression and reduces protein aggregation in various neurodegenerative variant models.
In order to identify disease modification genes that may explain the neuroprotective effects of XBP1 defects, we analyzed the gene expression spectrum of the cortical and symposomes of these animals and found that insulin-like growth factor 2 (IGF2) was the primary upward gene.
, we looked at the effects of IGF2 signals on protein aggregation in the Huntington's disease (HD) model.
cell culture studies have shown that IGF2 treatment reduces the load on in-cell aggregates of mutant Huntington proteins and polyglutamine peptides.
these results were validated with moderate spinal neurons derived from hemodialysis patients and patients with spinal co-cerebrocephalus disorders derived from induced cymbal stem cells (iPSCs).
levels of the mutant Huntington's protein was associated with a reduction in the half-life of the in-cell protein.
levels of abnormal protein aggregation caused by IGF2 were independent of autophagy activity and protease pathways, which are the two main pathways for the removal of mutant Huntington's proteins.
, the IGF2 signal enhances the secretion of the soluble mutant Huntington protein species by involving external bodies and microbuses involved in dynamic changes in the movement of the crest protein.
used gene therapy to inject IGF2 into the brains of high-density mice, resulting in significantly lower levels of the mutant Huntington's protein in three different animal models.
, analysis of brain tissue and blood samples after death showed a decrease in IGF2 levels in the blood.
study determined that IGF2 is a related factor in HD that can act as a disease regulator to cushion the accumulation of abnormal proteins.
method: Get Neuro2a and HEK293T cells from ATCC, add 5% fetal bovine serum and penicillin/streptomycin (Gibco) and store them in Dulbecco's improved Eagles medium.
3×105 cells were inoculated in a 6-well plate and stored for a prescribed time in a DMEM cell medium with 5% bovine serum and nonsteroidal amino acids added.
usually treated with autophagy, proteases, or cell vomit inhibitors for 16 hours, unless otherwise noted.
, our study suggests that IGF2 is an interesting disease regulator and an interesting candidate for the treatment of hemodialysis.
because IGF2 is a soluble factor, developing gene transfer strategies to improve IGF2 levels in the brain may be an attractive way to develop future treatments.
García-Huerta, P., Troncoso-Escudero, P., Wu, D. et al. Insulin-like growth factor 2 (IGF2) protects against Huntington's disease through the extracell disposalular of protein aggregates. Acta Neuropathol 140, 737-764 (2020). MedSci Original Source: MedSci Original Copyright Notice: All text, images and audio and video materials on this website that indicate "Source: Mets Medicine" or "Source: MedSci Original" are owned by Mets Medicine and are not authorized to be reproduced by any media, website or individual, and are authorized to be reproduced with the words "Source: Mets Medicine".
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