Telomere shortening leads to an acceleration of synucleinopathy and impaired microglia response in a genetic mouse model

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Abstract: Parkinson’s disease is one of the most common neurodegenerative disorders of the elderly and ageing hence described to be a major risk factor. Telomere shortening as a result of the inability to fully replicate the ends of linear chromosomes is one of the hallmarks of ageing. The role of telomere dysfunction in neurological diseases and the ageing brain is not clarified and there is an ongoing discussion whether telomere shortening is linked to Parkinson’s disease. Here we studied a mouse model of Parkinson’s disease (Thy-1 [A30P] α-synuclein transgenic mouse model) in the background of telomere shortening (Terc knockout mouse model). α-synuclein transgenic mice with short telomeres (αSYNtg/tg G3Terc-/-) developed an accelerated disease with significantly decreased survival. This accelerated phenotype of mice with short telomeres was characterized by a declined motor performance and an increased formation of α-synuclein aggregates. Immunohistochemical analysis and mRNA expression studies revealed that the disease end-stage brain stem microglia showed an impaired response in αSYNtg/tg G3Terc-/- microglia animals. These results provide the first experimental data that telomere shortening accelerates α-synuclein pathology that is linked to limited microglia function in the brainstem

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Notes: Acta Neuropathologica Communications. 4 (2016), 87, DOI 10.1186/s40478-016-0364-x, issn: 2051-5960
IN COPYRIGHT http://rightsstatements.org/page/InC/1.0 rs

Keyword: Parkinson-Krankheit
Telomer
Mikroglia
Hirnkrankheit
Neuropsychiatrie
Nervenkrankheit

Event: Veröffentlichung

(where): Freiburg

(who): Universität

(when): 2016

Creator: Scheffold, Annika
Holtman, Inge R.
Dieni, Sandra
Biber, Knut

Contributor: Klinik für Psychiatrie und Psychotherapie. Freiburg im Breisgau
Albert-Ludwigs-Universität Freiburg. Medizinische Fakultät
Albert-Ludwigs-Universität Freiburg

DOI: 10.1186/s40478-016-0364-x

URN: urn:nbn:de:bsz:25-freidok-126367

Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 25.03.2025, 1:45 PM CET

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Associated

Scheffold, Annika
Holtman, Inge R.
Dieni, Sandra
Biber, Knut
Klinik für Psychiatrie und Psychotherapie. Freiburg im Breisgau
Albert-Ludwigs-Universität Freiburg. Medizinische Fakultät
Albert-Ludwigs-Universität Freiburg
Universität

Time of origin

2016

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Telomere shortening leads to an acceleration of synucleinopathy and impaired microglia response in a genetic mouse model

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Other Objects (12)

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Kif21a deficiency leads to impaired glomerular filtration barrier function

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Reduced mannosidase MAN1A1 expression leads to aberrant N-glycosylation and impaired survival in breast cancer

Acceleration, Manuskript

Telomere dysfunction in chronic lymphocytic leukemia

Chronic kidney disease leads to inflammation in the brain via microglia activation : PhD thesis Silke Zimmermann

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Novel telomere binding proteins

Acceleration

Reduced mannosidase MAN1A1 expression leads to aberrant N-glycosylation and impaired survival in breast cancer

Acceleration, Manuskript

Telomere dysfunction in chronic lymphocytic leukemia

Chronic kidney disease leads to inflammation in the brain via microglia activation : PhD thesis Silke Zimmermann

Loss-Of HSPB8 leads to prolonged stress granules disassembly via impaired CASA-complex ultimately causing FUS-aggregation

Small circular DNAs for synthesis of the human telomere repeat : Varied sizes, structures and telomere-encoding activities

Telomere shortening in leukocyte subpopulations in depression

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Silencing of TGF[beta] signalling in microglia results in impaired homeostasis

Kif21a deficiency leads to impaired glomerular filtration barrier function

Novel telomere binding proteins

Acceleration

Reduced mannosidase MAN1A1 expression leads to aberrant N-glycosylation and impaired survival in breast cancer

Acceleration, Manuskript

Telomere dysfunction in chronic lymphocytic leukemia

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Telomere bei Aortenklappenstenosen und kathetergestütztem Aortenklappenersatz (TAVI)

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