A large scale analyses of neuronal proteins sheds light on the mechanisms underlying neurodegenerative disease.
One of the early signs of diseases like Alzheimer’s or Parkinson’s is that the junctions between nerve cells – called synapses – are damaged, thereby disrupting neuronal communication. A new molecular genetic study provides insights into what may make synapses so vulnerable.
For the first time researchers have used proteomics to profile the protein content of differentially vulnerable synapses in a mouse model of a juvenile form of a degenerative disorder called neuronal ceroid lipofuscinosis (NCL). The term NCL encompasses a group of disorders which collectively represent the most frequent form of dementia in childhood.
The authors found that perturbations in signalling pathways involved in the degradation of the amino acid valine and the rearrangement of the cytoskeleton correlate with synaptic vulnerability.
Their results show that combining genetic and pharmacological targeting of key signalling proteins at an early stage of disease progression in simplistic model systems can contribute to further our understanding of the mechanisms underlying neurodegenerative disease and identify new potential therapeutic targets for future examination.
This study represents further proof of principle that an approach combining such disparate tools and techniques is likely to provide, and is potentially necessary for, identification of novel factors which are capable of regulating the stability of the nervous system in health and disease.
The work – published in the journal Scientific Reports – was carried out by researchers from The Roslin Institute, Centre for Integrative Physiology and Euan MacDonald Centre for Motor Neurone Disease Research – University of Edinburgh, Institute for Science and Technology in Medicine - Keele University, Psychology & Neuroscience - King’s College London, and Los Angeles Biomedical Research Institute and David Geffen School of Medicine - University of California Los Angeles.
The study was supported by the Biotechnology and Biological Sciences Research Council, the Euan MacDonald Centre, The Darwin Trust of Edinburgh, the Batten Disease Support and Research Association and the RJAH Institute of Orthopaedics.
Maica Llavero Hurtado, Heidi R. Fuller, Andrew M. S. Wong, Samantha L. Eaton, Thomas H. Gillingwater, Giuseppa Pennetta, Jonathan D. Cooper & Thomas M. Wishart (2017) Proteomic mapping of differentially vulnerable pre-synaptic populations identifies regulators of neuronal stability in vivo. Scientific Reports 7, 12412. DOI: 10.1038/s41598-017-12603-0
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