On the distribution of intranuclear and cytoplasmic aggregates in the brainstem of patients with spinocerebellar ataxia type 2 and 3
| Autor: | Béla Melegh, Ewout R. Brunt, Mohamed Bouzrou, Horst-Werner Korf, Jeroen J de Vries, Michaela Fredrich, Kay Seidel, Georg Auburger, Wilfred F. A. den Dunnen, Udo Rüb, Inci Özerden, Sonny Siswanto |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
congenital hereditary and neonatal diseases and abnormalities Pathology medicine.medical_specialty Huntingtin General Neuroscience Neurodegeneration Context (language use) Protein aggregation Biology medicine.disease Pathology and Forensic Medicine 03 medical and health sciences Cell nucleus 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure medicine Spinocerebellar ataxia Neurology (clinical) Brainstem Trinucleotide repeat expansion 030217 neurology & neurosurgery |
| Zdroj: | Brain Pathology. 27:345-355 |
| ISSN: | 1015-6305 |
| DOI: | 10.1111/bpa.12412 |
| Popis: | The polyglutamine (polyQ) diseases are a group of genetically and clinically heterogeneous neurodegenerative diseases, characterized by the expansion of polyQ sequences in unrelated disease proteins, which form different types of neuronal aggregates. The aim of this study was to characterize the aggregation pathology in the brainstem of spinocerebellar ataxia type 2 (SCA2) and 3 (SCA3) patients. For good recognition of neurodegeneration and rare aggregates, we employed 100 µm PEG embedded brainstem sections, which were immunostained with the 1C2 antibody, targeted at polyQ expansions, or with an antibody against p62, a reliable marker of protein aggregates. Brainstem areas were scored semiquantitatively for neurodegeneration, severity of granular cytoplasmic staining (GCS) and frequency of neuronal nuclear inclusions (NNI). SCA2 and SCA3 tissue exhibited the same aggregate types and similar staining patterns. Several brainstem areas showed statistically significant differences between disease groups, whereby SCA2 showed more severe GCS and SCA3 showed more numerous NNI. We observed a positive correlation between GCS severity and neurodegeneration in SCA2 and SCA3 and an inverse correlation between the frequency of NNI and neurodegeneration in SCA3. Although their respective disease proteins are unrelated, SCA2 and SCA3 showed the same aggregate types. Apparently, the polyQ sequence alone is sufficient as a driver of protein aggregation. This is then modified by protein context and intrinsic properties of neuronal populations. The severity of GCS was the best predictor of neurodegeneration in both disorders, while the inverse correlation of neurodegeneration and NNI in SCA3 tissue implies a protective role of these aggregates. |
| Databáze: | OpenAIRE |
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