Subject(s)
Brain/diagnostic imaging , Lyme Neuroborreliosis/diagnosis , Meningitis, Bacterial/diagnosis , Myelitis/diagnosis , Spinal Cord/diagnostic imaging , Administration, Intravenous , Adolescent , Anti-Bacterial Agents/therapeutic use , Ceftriaxone/therapeutic use , Central Nervous System Viral Diseases/diagnosis , Diagnosis, Differential , Diarrhea , Flushing/physiopathology , Guillain-Barre Syndrome/diagnosis , Headache/physiopathology , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Irritable Mood , Lyme Neuroborreliosis/cerebrospinal fluid , Lyme Neuroborreliosis/physiopathology , Lyme Neuroborreliosis/therapy , Magnetic Resonance Imaging , Male , Meningitis, Bacterial/cerebrospinal fluid , Meningitis, Bacterial/physiopathology , Meningitis, Bacterial/therapy , Myelitis/cerebrospinal fluid , Myelitis/physiopathology , Myelitis/therapy , Neck Pain/physiopathology , Paresthesia/physiopathology , Peroneal Neuropathies/physiopathology , Pneumonia, Bacterial , Reflex, Abnormal , Sweating , Urinary Retention/physiopathology , West Nile Fever/diagnosisABSTRACT
The restoration of myelin sheaths on demyelinated axons remains a major obstacle in the treatment of multiple sclerosis (MS). Currently approved therapies work by modulating the immune system to reduce the number and rate of lesion formation but are only partially effective since they are not able to restore lost myelin. In the healthy CNS, myelin continues to be generated throughout life and spontaneous remyelination occurs readily in response to insults. In patients with MS, however, remyelination eventually fails, at least in part as a result of a failure of oligodendrocyte precursor cell (OPC) differentiation and the subsequent production of new myelin. A better understanding of the molecular mechanisms and signaling pathways that drive the process of myelin sheath formation is therefore important in order to speed the development of novel therapeutics designed to target remyelination. Here we review data supporting critical roles for three highly conserved intracellular signaling pathways: Wnt/ß-catenin, PI3K/AKT/mTOR, and ERK/MAPK in the regulation of OPC differentiation and myelination both during development and in remyelination. Potential points of crosstalk between the three pathways and important areas for future research are also discussed.