Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, which mainly affects the neurons of the motor system and leads to death typically within 5 years after symptoms onset. Since for this pathology there is still an urgent need of effective treatments, this project aimed at identifying novel therapeutic targets within the synaptic compartment. The combinatorial analysis of post mortem samples and cultured human motor neurons differentiated from hiPSCs highlighted a profound alteration affecting the machinery of synaptic vesicle release in ALS. Importantly, rescue of the synaptic aberration through treatment with docosahexaenoic acid also improved neuronal survival, highlighting the synapse as a potential therapeutic target in ALS.
Amr Aly, Zsofia I. Laszlo, Sandeep Rajkumar, Tugba Demir, Nicole Hindley, Douglas J. Lamont, Johannes Lehmann, Mira Seidel, Daniel Sommer, Mirita Franz-Wachtel, Francesca Barletta, Simon Heumos, Stefan Czemmel, Edor Kabashi, Albert Ludolph, Tobias M. Boeckers, Christopher M. Henstridge & Alberto Catanese. Integrative proteomics highlight presynaptic alterations and c-Jun misactivation as convergent pathomechanisms in ALS. Acta Neuropathologica. 24. July 2023.
Submitting the Paper of the Month:
Else Kröner-Fresenius-Stiftung is using the series “Paper of the Month” to report in an exemplary and hot-off-the-press style on the outstanding work being done by the scientists it supports. We regularly present publications which have recently appeared in especially renowned journals, have emerged from foundation funding and been given appropriate acknowledgment. This is done in the respective categories “Original Paper” and “Review”. In the case of each of these publications, the first author and/or senior author are being funded by the foundation.
We invite all project managers, fellowship recipients and members of graduate study programs to send their work in accordance with the stated criteria as proposal for Paper of the Month to Ms. Anne Asschenfeldt (firstname.lastname@example.org).