How aggregates of polyglutamine proteins are involved in the neurological symptoms of glutamine repeat diseases is unknown. We show that huntingtin aggregates are present in the neuronal processes of transgenic mice that express exon 1 of the Huntington's disease (HD) gene. Unlike aggregates in the nucleus, these neuropil aggregates are usually smaller and are not ubiquitinated. Electron microscopy reveals many neuropil aggregates in axons and axon terminals. Huntingtin aggregates in the axon terminal are co-localized with some synaptic vesicles, implying that they may affect synaptic transmission and neuronal communication. The formation of neuropil aggregates is highly correlated with the development of neurological symptoms. The present study raises the possibility that neuropil aggregates may cause a dysfunction in neuronal communication and con-tribute to the neurological symptoms of HD.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/hmg/8.7.1227 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Background: Phosphorylated tau proteins accumulate in pathological aggregates which define neurodegenerative tauopathies, including Alzheimer's disease (AD). Insight into the early stages of tau polymerization/aggregation, including early hyperphosphorylation events, is critical for identification of biomarkers of incipient disease as well as novel therapy targets.
Method: We analyzed postmortem tissue sections of hippocampus from AD cases and middle frontal gyrus from non-AD cases with mainly 4R tau isoforms (progressive supranuclear palsy, PSP; corticobasal degeneration, CBD; aging related tau astrogliopathy, ARTAG) or 3R tau (Pick's disease, PiD).
Background: Hyperphosphorylation and aggregation of neuronal tau protein is a primary pathological hallmark of Alzheimer's disease (AD) and primary tauopathies. The accumulation of aggregated tau as neurofibrillary tangles (NFTs) is closely correlated with neurodegeneration and cognitive decline. Key phosphorylation sites on tau have been established as early biomarkers for disease detection and prediction, with various phosphorylation sites differentially appearing across diseases and disease stages.
View Article and Find Full Text PDFH3 K27-altered diffuse midline glioma of the thalamus with formation of glio-fibrillary globular structures.
Int J Clin Exp Pathol
July 2024
Department of Pathology, Kansai Medical University Hospital Hirakata, Osaka, Japan.
A case of diffuse midline glioma (DMG), H3 K27-altered, that arose in the right thalamus of a 14-year-old boy is reported. The patient died of tumor spread after a progressive clinical course of approximately 13 months. Histopathologically, the tumor consisted of a mixture of loose proliferation of stellate cells and compact fascicular growth of spindle cells showing a "piloid" feature.
View Article and Find Full Text PDFUnlabelled: Modifiers of Huntington's disease (HD) include mismatch repair (MMR) genes; however, their underlying disease-altering mechanisms remain unresolved. Knockout (KO) alleles for 9 HD GWAS modifiers/MMR genes were crossed to the Q140 Huntingtin (mHtt) knock-in mice to probe such mechanisms. Four KO mice strongly ( and ) or moderately ( and ) rescue a triad of adult-onset, striatal medium-spiny-neuron (MSN)-selective phenotypes: somatic DNA CAG-repeat expansion, transcriptionopathy, and mHtt protein aggregation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!