CONTEXT

The cerebrospinal fluid (CSF) is a sample of choice for biomarker discovery. However, proteomic approaches have been met with limited success due to the difficulty in identifying in CSF samples proteins that truly originate from neurons and that actually reflect neuronal dysfunction or death. Although apoptosis is a major mechanism of neuronal death in many neurodegenerative disorders, apoptotic neurons are often sparse in the brain of patients, making even more uncertain the identification of biomarkers of neuronal apoptosis in CSF.
Neuroregeneration, contrary to neurodegeneration, refers to the neuronal multiplication or differentiation or the synaptogenesis. Such mechanisms may include generation of new neurons, glia, axons, myelin, or synapses. So far, only a few biomarkers of neurogenesis are known.
The increasing frequency of neurodegenerative diseases and the lack of early and specific diagnostic and prognostic biomarkers necessitate the discovery of such new biomarkers of these diseases as well as biomarker for neurogenesis.

TECHNICAL DESCRIPTION

Stable isotope labeling by/with amino acids in cell culture (SILAC) is a technique based on mass spectrometry that detects differences in protein abundance among samples using non-radioactive isotopic labeling. Adapting this technique to detect neuronal secretome, Marin et al. have found that the extra cellular soluble part of the (pro)renin receptor (sPRR) was one of the proteins most differentially expressed in supernatants of apoptotic and surviving neurons.
Indeed, sPRR level was found elevated in conditioned medium of living neurons in culture, while decreased in the conditioned medium of dying neurons. Preliminary results from the co-inventors groups show that sPRR can be measured in CSF.

DEVELOPMENT STAGE

CSF from patients having various neurodegenerative diseases are currently being tested.

INDUSTRIAL APPLICATIONS

These biomarkers are to be used for the diagnostic and/or prognosis of neurodegenerative diseases, in particular Alzheimer’s disease, dementia with Lewy bodies, fronto-temporal dementia, Parkinson’s disease, amyotrophic lateral sclerosis, as well as for the follow up of neurodegenerative diseases treatments.
Conversely, they may be used for the diagnostic and/or prognosis of diseases implicating a neuronal proliferation, such as glioblastomas, as well as for the follow-up of their  antiproliferative treatments.
Last, these biomarkers may be useful for the screening of new compounds liable to treat neurodegenerative diseases and to assess the efficacy of neuropsychiatric drugs.

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