Grant: Foundation Grant

Alzheimer'S Disease; Immunotherapy; Innate Immunity; Microglia; Monocytes; Multiple Sclerosis; Neuroinflammation; Neuroprotection; Preclinical Mouse Models; The Neurovascular Unit

<html> <body> <p>We have played a key role in the characterization of the CNS innate immune mechanisms. While potentially detrimental in some cases, innate immunity remains the first line of defense against insults. The overarching goal of our research program has been to decipher this role and, most importantly, how this system can be harnessed in therapeutic settings for brain diseases. The inflammatory response has often been linked to progressive neuronal damage in neurodegenerative diseases. However, mounting evidence now suggests that CNS-resident microglia and circulating monocytes that differentiate into macrophages upon infiltrating the brain parenchyma may be more beneficial to neurons than previously thought. Multiple sclerosis (MS) and Alzheimer&rsquo;s disease (AD), which are often compared as brain diseases with similar immune etiologies, provide clear examples of the disease-dependent and dual nature of the innate immune system in the brain. In that regard they indeed show a &ldquo;Yin/Yang&rdquo; opposition. Thus, whereas the marked and sustained activation of proinflammatory monocytic cells contributes to demyelination and axonal loss in MS, on the other hand, it is the anti-inflammatory (or inactivated) phenotype of monocytic cells which allows amyloid-&#x03b2; accumulation in the CNS, neuronal dysfunction and memory decline in AD. This research program is dedicated to elucidate in depth the mechanistic details of the role of the innate immune system in the CNS and to determine how one can rein in its potential to have a neuroprotective action in two highly divergent brain diseases, namely MS and AD.<br> <br> Our main <u>goals</u> are to provide new biomarkers for diagnosis and to obtain proofs-of-concept that will lead to new treatments of brain diseases based on the neuroprotective functions of innate immunity.<br> <br> <u>Objectives:</u> 1) To decipher the molecular and cellular mechanisms involved in the fine control of the various compartments of the brain innate immune system. 2) To identify new biomarkers from the analysis of subsets of circulating monocytes in preclinical models of MS and AD. 3) To use and develop complementary models and technologies to understand how myeloid cells can be tackled to exhibit neuroprotective properties. 4) To validate new biomarkers and concepts of the beneficial role of the innate immune system in humans. This research program will <u>accelerate</u> the development of new diagnostic tools and treatments of AD and MS.<br> <br> Our expertise at deciphering the complexity of the brain innate immune system and its role in various physiological and pathological conditions is widely recognized. This expertise also includes the development of new mouse models of brain diseases and injuries, new techniques for the imaging of the movements and interactions of immune cells in the brain of live mice and the creation of an exceptional training environment. In addition to a very innovative research program combining immunology, molecular neurobiology, stem cells, immunotherapy, gene expression profiling and genome editing, our students will benefit from state-of-the-art infrastructures and platforms, which will train them with the most cutting-edge techniques and approaches. This major research program will provide a superior, multidisciplinary experience for trainees in an area that is crucial for Canada, which will help to meet the demand for highly skilled researchers and professionals in universities, research institutes, hospitals, pharmaceutical and biotech companies.</p> </body> </html>