High-resolution imaging of synaptic integrity in MND

About the project

Synapse loss is an early feature of most neurodegenerative diseases, including MND, yet we do not have a clear understanding of the underlying mechanisms. By using high-resolution imaging and proteomic screening, we hope to identify the mechanisms driving synapse loss in MND and highlight potential new therapeutic targets. We have shown that synapse loss occurs in the frontal cortex of some MND patients and greater synapse loss associates with poorer cognitive function. To build on this, we are now running unbiased proteomic screening of synaptically-enriched human brain fractions to identify the pathways and proteins that are disrupted in MND. These exciting new targets will be validated in human tissue before moving into model systems to assess their role on synaptic toxicity.

Funder(s)

MND Scotland, RS MacDonald Trust, Euan MacDonald Centre, Tenovus Scotland, Alzheimer's Society, Alzheimer's Research UK, Academy of Medical Sciences, the Neurosciences Foundation, MND Association

Publication(s)

Henstridge CM, Sideris DI, Carroll E, Rotariu S, Salomonsson S, Tzioras M et al.
Synapse loss in the prefrontal cortex is associated with cognitive decline in amyotrophic lateral sclerosis.
Acta Neuropathologica. 2018 Feb;135(2):213-226.
2019 Jun 18
Zsofia I Laszlo, Nicole Hindley, Anna Sanchez Avila, Rachel A Cline, Samantha L Eaton, Douglas J Lamont, Colin Smith, Tara L Spires-Jones, Thomas M Wishart, Christopher M Henstridge
Synaptic proteomics reveal distinct molecular signatures of cognitive change and C9ORF72 repeat expansion in the human ALS cortex
Acta Neuropatholica Communications
2022 Oct 29
Amr Aly, Zsofia I Laszlo, Sandeep Rajkumar, Tugba Demir, Nicole Hindley, Douglas J Lamont, Joannes Lehmann, Mira Seidel, Daniel Sommer, Mirita Franz-Wachtel, Francesca Barletta, Simon Heumos
Stefan Czemmel, Edor Kabashi, Albert Ludolph, Tobias M Boeckers, Christopher M Hensstridge, Alberto Catanese
Integrative proteomics highlight presynaptic alterations and c-Jun misactivation as convergent pathomechanisms in ALS
Acta Neuropathologica Communications
2023 Jul 24

Primary location

Dundee
×