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26.08.2019 | Original Paper

Early defects in translation elongation factor 1α levels at excitatory synapses in α-synucleinopathy

verfasst von: Sonja Blumenstock, Maria Florencia Angelo, Finn Peters, Mario M. Dorostkar, Viktoria C. Ruf, Manja Luckner, Sophie Crux, Lenka Slapakova, Thomas Arzberger, Stéphane Claverol, Etienne Herzog, Jochen Herms

Erschienen in: Acta Neuropathologica | Ausgabe 6/2019

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Abstract

Cognitive decline and dementia in neurodegenerative diseases are associated with synapse dysfunction and loss, which may precede neuron loss by several years. While misfolded and aggregated α-synuclein is recognized in the disease progression of synucleinopathies, the nature of glutamatergic synapse dysfunction and loss remains incompletely understood. Using fluorescence-activated synaptosome sorting (FASS), we enriched excitatory glutamatergic synaptosomes from mice overexpressing human alpha-synuclein (h-αS) and wild-type littermates to unprecedented purity. Subsequent label-free proteomic quantification revealed a set of proteins differentially expressed upon human alpha-synuclein overexpression. These include overrepresented proteins involved in the synaptic vesicle cycle, ER–Golgi trafficking, metabolism and cytoskeleton. Unexpectedly, we found and validated a steep reduction of eukaryotic translation elongation factor 1 alpha (eEF1A1) levels in excitatory synapses at early stages of h-αS mouse model pathology. While eEF1A1 reduction correlated with the loss of postsynapses, its immunoreactivity was found on both sides of excitatory synapses. Moreover, we observed a reduction in eEF1A1 immunoreactivity in the cingulate gyrus neuropil of patients with Lewy body disease along with a reduction in PSD95 levels. Altogether, our results suggest a link between structural impairments underlying cognitive decline in neurodegenerative disorders and local synaptic defects. eEF1A1 may therefore represent a limiting factor to synapse maintenance.

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Titel: Early defects in translation elongation factor 1α levels at excitatory synapses in α-synucleinopathy
verfasst von: Sonja Blumenstock
Maria Florencia Angelo
Finn Peters
Mario M. Dorostkar
Viktoria C. Ruf
Manja Luckner
Sophie Crux
Lenka Slapakova
Thomas Arzberger
Stéphane Claverol
Etienne Herzog
Jochen Herms
Publikationsdatum: 26.08.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Acta Neuropathologica / Ausgabe 6/2019
Print ISSN: 0001-6322
Elektronische ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-019-02063-3

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Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Viel Bewegung in der Parkinsonforschung

25.04.2024 Parkinson-Krankheit Nachrichten

Neue arznei- und zellbasierte Ansätze, Frühdiagnose mit Bewegungssensoren, Rückenmarkstimulation gegen Gehblockaden – in der Parkinsonforschung tut sich einiges. Auf dem Deutschen Parkinsonkongress ging es auch viel um technische Innovationen.

Demenzkranke durch Antipsychotika vielfach gefährdet

23.04.2024 Demenz Nachrichten

Wenn Demenzkranke aufgrund von Symptomen wie Agitation oder Aggressivität mit Antipsychotika behandelt werden, sind damit offenbar noch mehr Risiken verbunden als bislang angenommen.

Update Neurologie

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