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- Huang, Ting TingNortheastern University (författare)
No symphony without bassoon and piccolo : Changes in synaptic active zone proteins in Huntington's disease
- Artikel/kapitelEngelska2020
Förlag, utgivningsår, omfång ...
- 2020-06-03
- Springer Science and Business Media LLC,2020
Nummerbeteckningar
- LIBRIS-ID:oai:lup.lub.lu.se:82850ad9-296d-47a1-aecc-2f5438f234c5
- https://lup.lub.lu.se/record/82850ad9-296d-47a1-aecc-2f5438f234c5URI
- https://doi.org/10.1186/s40478-020-00949-yDOI
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- Språk:engelska
- Sammanfattning på:engelska
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- Prominent features of HD neuropathology are the intranuclear and cytoplasmic inclusions of huntingtin and striatal and cortical neuronal cell death. Recently, synaptic defects have been reported on HD-related studies, including impairment of neurotransmitter release and alterations of synaptic components. However, the definite characteristics of synapse dysfunction and the underlying mechanisms remain largely unknown. We studied the gene expression levels and patterns of a number of proteins forming the cytoskeletal matrix of the presynaptic active zones in HD transgenic mice (R6/1), in hippocampal neuronal cultures overexpressing mutant huntingtin and in postmortem brain tissues of HD patients. To investigate the interactions between huntingtin and active proteins, we performed confocal microscopic imaging and immunoprecipitation in mouse and HEK 293 cell line models. The mRNA and protein levels of Bassoon were reduced in mouse and cell culture models of HD and in brain tissues of patients with HD. Moreover, a striking re-distribution of a complex of proteins including Bassoon, Piccolo and Munc 13-1 from the cytoplasm and synapses into intranuclear huntingtin aggregates with loss of active zone proteins and dendritic spines. This re-localization was age-dependent and coincided with the formation of huntingtin aggregates. Using co-immunoprecipitation, we demonstrated that huntingtin interacts with Bassoon, and that this interaction is likely mediated by a third linking protein. Three structural proteins involved in neurotransmitter release in the presynaptic active zones of neurons are altered in expression and that the proteins are redistributed from their normal functional site into mutant huntingtin aggregates.
Ämnesord och genrebeteckningar
- MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Neurologi hsv//swe
- MEDICAL AND HEALTH SCIENCES Clinical Medicine Neurology hsv//eng
- Active zone proteins
- Huntington's disease
- Protein aggregation
- Synaptic dysfunction
Biuppslag (personer, institutioner, konferenser, titlar ...)
- Smith, RubenLund University,Lunds universitet,Regeneration in Movement Disorders,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital(Swepub:lu)mphy-rsm (författare)
- Bacos, KarlLund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups(Swepub:lu)medk-kb0 (författare)
- Song, Dong YanNortheastern University (författare)
- Faull, Richard M.University of Auckland (författare)
- Waldvogel, Henry J.University of Auckland (författare)
- Li, Jia YiLund University,Lunds universitet,Neural plasticitet och reparation,Forskargrupper vid Lunds universitet,Neural Plasticity and Repair,Lund University Research Groups,China Medical University, Shenyang,Northeastern University(Swepub:lu)mphy-jli (författare)
- Northeastern UniversityRegeneration in Movement Disorders (creator_code:org_t)
Sammanhörande titlar
- Ingår i:Acta Neuropathologica Communications: Springer Science and Business Media LLC8:12051-5960
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- Acta Neuropathologica Communications (Sök värdpublikationen i LIBRIS)
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- Li, Jia Yi
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