{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:17:30Z","timestamp":1791919050552,"version":"4.3.4"},"reference-count":54,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,7,2]],"date-time":"2015-07-02T00:00:00Z","timestamp":1435795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Dr. Senckenbergische Stiftung"},{"name":"ADCA-Vereniging Nederland"},{"name":"Stiftung Hoffnung"},{"name":"Deutsche Huntington Hilfe"},{"name":"deutsche Heredo-Ataxie Gesellschaft"},{"name":"International Stichting Alzheimer Onderzoek","award":["09514"],"award-info":[{"award-number":["09514"]}]},{"name":"Hersenstichting Nederland grant","award":["# F2012(1)-104"],"award-info":[{"award-number":["# F2012(1)-104"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Polyglutamine (<jats:styled-content style=\"fixed-case\">polyQ<\/jats:styled-content>) diseases are characterized by the expansion of a polymorphic glutamine sequence in disease\u2010specific proteins and exhibit aggregation of these proteins. This is combated by the cellular protein quality control (<jats:styled-content style=\"fixed-case\">PQC<\/jats:styled-content>) system, consisting of chaperone\u2010mediated refolding as well as proteasomal and lysosomal degradation pathways. Our recent study in the<jats:styled-content style=\"fixed-case\">polyQ<\/jats:styled-content>disease spinocerebellar ataxia type 3 (<jats:styled-content style=\"fixed-case\">SCA3<\/jats:styled-content>) suggested a distinct pattern of protein aggregation and<jats:styled-content style=\"fixed-case\">PQC<\/jats:styled-content>dysregulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To corroborate these findings we have investigated immunohistochemically stained 5\u2009\u03bcm sections from different brain areas of<jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>untington's disease (<jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>) and<jats:styled-content style=\"fixed-case\">SCA3<\/jats:styled-content>patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Irrespective of disease and brain region, we observed peri\u2010 and intranuclear<jats:styled-content style=\"fixed-case\">polyQ<\/jats:styled-content>protein aggregates. A subset of neurones with intranuclear inclusions bodies exhibited signs of proteasomal dysfunction, up\u2010regulation of<jats:styled-content style=\"fixed-case\">HSPA1A<\/jats:styled-content>and re\u2010distribution of<jats:styled-content style=\"fixed-case\">DNAJB1<\/jats:styled-content>. The extent of the observed effects varied depending on brain area and disease protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results suggest a common sequence, in which formation of cytoplasmic and nuclear inclusions precede proteasomal impairment and induction of the cellular stress response. Clearly, impairment of the<jats:styled-content style=\"fixed-case\">PQC<\/jats:styled-content>is not the primary cause for inclusion formation, but rather a consequence that might contribute to neuronal dysfunction and death. Notably, the inclusion pathology is not directly correlated to the severity of the degeneration in different areas, implying that different populations of neurones respond to<jats:styled-content style=\"fixed-case\">polyQ<\/jats:styled-content>aggregation with varying efficacy and that protein aggregation outside the neuronal perikaryon (e.g. axonal aggregates) or other effects of<jats:styled-content style=\"fixed-case\">polyQ<\/jats:styled-content>aggregation, which are more difficult to visualize, may contribute to neurodegeneration.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12253","type":"journal-article","created":{"date-parts":[[2015,6,19]],"date-time":"2015-06-19T17:32:30Z","timestamp":1434735150000},"page":"153-166","source":"Crossref","is-referenced-by-count":47,"title":["Polyglutamine aggregation in<scp>H<\/scp>untington's disease and spinocerebellar ataxia type 3: similar mechanisms in aggregate formation"],"prefix":"10.1111","volume":"42","author":[{"given":"K.","family":"Seidel","sequence":"first","affiliation":[{"name":"Dr. Senckenbergisches Chronomedizinisches Institut Goethe University Frankfurt\/Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Siswanto","sequence":"additional","affiliation":[{"name":"Dr. Senckenbergisches Chronomedizinisches Institut Goethe University Frankfurt\/Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Fredrich","sequence":"additional","affiliation":[{"name":"Dr. Senckenbergisches Chronomedizinisches Institut Goethe University Frankfurt\/Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Bouzrou","sequence":"additional","affiliation":[{"name":"Dr. Senckenbergisches Chronomedizinisches Institut Goethe University Frankfurt\/Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. 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