The "dance steps" that stray RNA can't stop

!--webeditor: """"-misplaced RNA in the brain destroys neurons, allows people to lose control of their movements, and even develops Huntington's disease.
Neuroscientists at the Massachusetts Institute of Technology have found that the leading cause of neuronal death in huntington's disease may be an immune response to the abnormal release of genetic material from mitochondria.
mitochondria are the cellular components that provide energy.
study comprehensively tracked the different types of brain cells in how to respond to mutations that lead to Huntington's disease.
researchers measured the rna differences between brain samples and normal human stakes in patients who died of Huntington's disease in different cell types at different stages of disease development, and RNA levels in mice that had undergone different levels of genetic mutations.
papers were recently published in Neuron.
" mitochondria release these RNA escants that look like viral RNA, which triggers innate immunity and can lead to cell death. "We believe this is part of the pathway that triggers the signaling of inflammation," said Myriam Heiman, author of the study and associate professor of brain and cognitive sciences at the Massachusetts Institute of Technology.

" Huntington's disease, a degenerative disease caused by chromosomal dominant genetic strains, can ruthlessly rob victims of their ability to control movement and thought.
patients develop dance symptoms such as twitching and may eventually die prematurely.
globally, between 3 and 10 people per 100,000 people are affected by the disease and there is no cure.
named after George Huntington, an American physician who described the disease in 1872.
scientists have been exploring the disease for more than 100 years.
1993, scientists discovered that the genetic mutation that causes Huntington's disease is near the top of the short arm of chromosome 4.
no one knows how the mutated huntington's protein (mHTT) destroys neurons.
and even Huntington's disease is a late-stage neurodegenerative disease, but mouse studies and neuroimaging studies of carriers of pre-symptom mutations have shown that Huntington's disease may affect neurodevelopment. The study, published july 16 in Science,
, noted that the tissue that carries a mutation in Huntington's disease in human fetuses (13 weeks of pregnancy) shows significant abnormalities in the developing cortex, including mutations of Huntington's protein and the location of connected complex proteins, defects in the polarity and differentiation of neuroprogenocells, abnormal cilia, and processes of silk division and cell cycle changes.
, the researchers say, Huntington's disease has an effect on neurodevelopment, not just a degenerative disease.
However, "since the function of mutant proteins and the related mechanisms associated with disease are still unknown, traditional methods cannot be used to screen blockers for their pathological functions."
" said Lu Boxuan, a researcher at Fudan University's National Key Laboratory for Medical Neurobiology.
mitochondrial "accidents" to better explore the secrets of Huntington's disease, the Heiman team used two different screening techniques, TRAP can be used in mouse models, and single-core RNA sequencing can be used in mice and humans.
surprising finding, RNA in mitochondria is mistakenly placed in brain cells called stinging neurons (SPNs), destroying these neurons and causing fatal neurological symptoms.
the researchers observed that these free RNAs appear to differ in cells from rna extracted from the nucleus, triggering a problematic immune response.
, they not only discovered the presence of mitochondrial RNA, but also showed a lack of gene expression in the oxidation phosphorylation process, a process in which neurons that need fuel produce energy.
previously, mouse experiments showed that this reduction in oxidation phosphorylation and increased release of mitochondrial RNA occurred in the early stages of Huntington's disease, before most other gene expression differences appeared.
, the researchers also found an increased expression of an immune system protein called PKR, which proved to be a sensor for releasing mitochondrial RNA.
in fact, the team found that PKR not only rises in neurons, but is activated and binds to mitochondrial RNA.
Heiman says the new findings appear to be consistent with some clinical symptoms.
, for example, Huntington's disease causes damage to the striatum region of the brain; in Aicardi-Gouti?res syndrome, the same brain region may be damaged by congenital immune disorders; and children with thiamine deficiency have mitochondrial dysfunction, and studies have shown that their mouse models also exhibit PKR activation.
" the paper's biggest highlight is the histological section, which should be the first histological study using single-cell (monocore) sequencing and TRAP (measuring mRNAs being translated).
" Lu, who was not involved in the study, told China Science Daily.
, who may have learned from the clinical, said they also found significant differences in gene expression, including differences related to important neural functions, such as synaptic circuit connections and biological clock functions.
, the team found that the main regulatory factor for these gene transcription changes in neurons may be the retinal acid receptor b transcription factor.
"This may be a clinically useful finding because there are drugs that can activate Rarb."
," Heiman told China Science Daily.
this is an important assumption that needs to be validated.
", on the other hand, many of the differences in gene expression that the researchers saw in neurons in human brain samples were very consistent with the changes they saw in mouse neurons, further ensuring that mouse models were useful for studying the disease.
the problem has been plaguing the field, because mice don't usually die as many neurons as humans do. "What we're seeing
is that the mouse model actually reproduces the gene expression changes that occurred well in the neurons that occurred during the Huntington's disease in humans.
but some other non-neuronal cell types don't show much conservatism between human disease and mouse models, and we believe this information will help other researchers with future research.
," Heiman said.
actually, in addition to mouse models, pigs are also "contributing" to research in this field.
2018, researchers used gene-editing technology CRISPR-Cas9 and somatic cell nuclei transplanttechnologforably to create the world's first Huntington's disease gene knockout into a pig, which accurately simulates human neurodegenerative disease.
!--/ewebeditor:!--:page:page title"-- In addition, in 2019, the Lubber team pioneered the development of original concepts for drugs based on autophagy-binding compounds, and cleverly discovered small molecule compounds that reduce specificity to Huntington's disease-causing proteins through screening based on compound chips and cutting-edge optical methods, promising to bring new light to clinical treatment.
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