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eEF1α: a new synaptic player in Synucleinopathies - Acta Neuropathologica, August 2019

Thursday 29 August 2019, by Marie-Noelle Gouineau

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

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 over-expressing human alpha-synuclein (h-αS) and wild-type littermates to unprecedented purity. Subsequent label-free prot-eomic 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 neuro-degenerative disorders and local synaptic defects. eEF1A1 may therefore represent a limiting factor to synapse maintenance.

Identification of the protein eEF1α at purified excitatory presynapses

Sonja Blumenstock, Maria-Florencia Angelo, Finn Peters, Mario M Dorotskar, Viktoria C. Ruf, Manja Luckner, Sophie Cruz, Lenka Slapakova, Thoma Arzberger, Stéphane Claverol, Etienne Herzog, Jochen Herms.

- Acta Neuropathologica.
- More details here
- Contact: Etienne Herzog, IINS

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