Science: Huntington's disease alters human neurodevelopment.

July 17, 2020 /PRNewswire/ -- --- Huntington's disease (HUNTINGTON's disease, HD) is one of the four major neurodegenerative diseases that have been studied most widelyThe disease is caused by mutations in the huntingtin (HTT) encoded genePeople with HD experience depression, irritability, and other neurological and behavioral problemsThey may also have difficulty processing information and controlling body movementsAlthough HD is a late-stage neurodegenerative disease, mouse studies and neuroimaging studies of carriers of pre-symptom mutations have shown that the disease may affect neurodevelopmentTo determine whether this is really the case, in a new study, researchers from France studied tissue from human fetuses carrying HD mutations (13 weeks of pregnancy)The findings were published online July 16, 2020 in the journal Science, under the title "Huntington's disease alters human neurodevelopment"HTT mutation and basal nucleus (basal ganglia)HD disease is caused by the amplification of polyglutamine encoded by CAG repeat sequencesThe base core is the most serious site in HD patientsPhoto from Translational Neurodegeneration, 2017, doi:10.1186/s40035-017-0101-9These tissues exhibit significant abnormalities in the developing cortex, including the mislocation of the mutated HTT protein and the connective complex protein, defects in the polarity and differentiation of neuroprogenitor cells, abnormal fibrosis, and changes in the process of filament and cell cyclesThe researchers observed the same phenomenon in the embryos of HD mice, linking these abnormalities to defects in the kinetic precursor cells' dynamic intercellular nuclear migration (INM)As a result, HD has a neurodevelopmental component, not just a degenerative diseaseIn this disease, nerve cells in the brain are destroyed over timeIt may become noticeable at any time in life, but usually begins in a person's thirties and fortiesHD and many other neurodegenerative diseases are caused by a repetitive sequence of CAGs that are genetically amplification, in which CAG crypts encode an amino acid called glutamineThe age of onset of these diseases was negatively correlated with the length of the amplification CAG repeat sequence and is thought to be due to increased toxicity of polyglutamine encoded in this CAG repeat sequence in DNAHowever, it has been found that the timing of HD incidence is due to the characteristics of the amplified CAG repeat sequence in the individual DNA, not due to the length of polyglutamamine (Cell, 2019, doi:10.1016/j.cell.2019.06.036)This key characteristic of CAG repeat sequence sdecreases because it tends to expand further as the individual ages, causing caG repeat sequences in specific brain cells to grow longer and longer until critical threshold lengths are reached and toxicTherefore, people should focus early on the process of the disease on the DNA repeat sequence itself rather than the protein it encodes(Bioon.com) References: Monia Barnat et alHuntington's disease alters human neurodevelopmentScience, 2020, doi: 10.1126/science.aax3338.