Neuropharmacology
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Microglia and neuroinflammation in the pathophysiology of CNS diseases In the central nervous system (CNS) microglia, the resident brain macrophages, are recognized as the prime component of the brain immune system. In the normal CNS, microglia play critical roles during development of the neuronal network and maintenance of brain homeostasis. | |
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In the central nervous system (CNS) microglia, the resident brain macrophages, are recognized as the prime component of the brain immune system. In the normal CNS, microglia play critical roles during development of the neuronal network and maintenance of brain homeostasis. However, changes in the microenvironment due to injury, stress or infection lead to microglial cell activation and the subsequent production of numerous cytokines and chemokines. While this inflammatory response is intended to remove toxins from the extracellular space, prolonged activation of microglia can trigger chronic neuroinflammation, neuronal cell degeneration and, ultimately, the death associated with neurodegenerative (Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis – among others) and psychiatric (psychosis, schizophrenia, depression) disorders.
Given the growing relevance of microglia and neuroinflammation in the study of neurological diseases, our research focuses on the role of microglia and the cellular mechanisms that activate these cells, as well as on the identification of novel molecules able to modulate or inhibit microglial activation and promote neuronal cell protection.
In this context, in vitro and in vivo models of neuroinflammation provide a valuable platform for testing the anti-inflammatory and potential neuroprotective effects of new chemical entities, with the ultimate goal of developing novel pharmacological treatments whose therapeutic target is neuroinflammation.
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Oligodendrocytes and demyelinating diseases Oligodendrocytes are the myelin-producing cells of the CNS. Myelin, a lipid-rich membrane, insulates the axons of neurons thereby allowing the rapid conduction of electrical impulses and delivery of the action potential to the target cell. Loss of myelin leads to a range of neurological disorders, including reduced motor function, impaired cognitive abilities, and vision problems. Among demyelinating diseases affecting the CNS, multiple sclerosis (MS) has probably received the most attention. | |
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Different therapeutic strategies are available for treatment of MS including immunosuppressants, immunomodulators, and monoclonal antibodies. Intended to target the recurring inflammation of the disease, they do not necessarily ensure remyelination. Our research is directed to the next phase of MS therapy, namely, remyelination/regeneration. Strategies intended to promote endogenous remyelination should focus on both enhancing the long-term survival of oligodendrocyte precursor cells and on stimulating these cells to proliferate and differentiate into remyelinating oligodendrocytes. Using cell culture systems based on isolated populations of oligodendrocyte precursor cells directed to proliferate or differentiate, we are exploring pharmacological agents capable of enhancing survival and maturation, respectively, of these two cell populations using immunocytochemical and molecular biological techniques. Results from this first phase are then advanced to the evaluation of suitable molecules to favor clinical outcome in animal models of MS, namely, experimental autoimmune encephalomyelitis.
