Modulation of the Microglial Nogo-A/NgR Signaling Pathway as a Therapeutic Target for Multiple Sclerosis
Danica Nheu,
Olivia Ellen,
Sining Ye,
Ezgi Ozturk,
Maurice Pagnin,
Stephen Kertadjaja,
Paschalis Theotokis,
Nikolaos Grigoriadis,
Catriona McLean,
Steven Petratos
Affiliations
Danica Nheu
Department of Neuroscience, Central Clinical School, Monash University, Prahran, VIC 3004, Australia
Olivia Ellen
Department of Neuroscience, Central Clinical School, Monash University, Prahran, VIC 3004, Australia
Sining Ye
Department of Neuroscience, Central Clinical School, Monash University, Prahran, VIC 3004, Australia
Ezgi Ozturk
Department of Neuroscience, Central Clinical School, Monash University, Prahran, VIC 3004, Australia
Maurice Pagnin
Department of Neuroscience, Central Clinical School, Monash University, Prahran, VIC 3004, Australia
Stephen Kertadjaja
Department of Neuroscience, Central Clinical School, Monash University, Prahran, VIC 3004, Australia
Paschalis Theotokis
Laboratory of Experimental Neurology and Neuroimmunology, Department of Neurology, AHEPA University Hospital, Stilponos Kiriakides str. 1, 54636 Thessaloniki, Greece
Nikolaos Grigoriadis
Laboratory of Experimental Neurology and Neuroimmunology, Department of Neurology, AHEPA University Hospital, Stilponos Kiriakides str. 1, 54636 Thessaloniki, Greece
Catriona McLean
Department of Anatomical Pathology, Alfred Hospital, Prahran, VIC 3004, Australia
Steven Petratos
Department of Neuroscience, Central Clinical School, Monash University, Prahran, VIC 3004, Australia
Current therapeutics targeting chronic phases of multiple sclerosis (MS) are considerably limited in reversing the neural damage resulting from repeated inflammation and demyelination insults in the multi-focal lesions. This inflammation is propagated by the activation of microglia, the endogenous immune cell aiding in the central nervous system homeostasis. Activated microglia may transition into polarized phenotypes; namely, the classically activated proinflammatory phenotype (previously categorized as M1) and the alternatively activated anti-inflammatory phenotype (previously, M2). These transitional microglial phenotypes are dynamic states, existing as a continuum. Shifting microglial polarization to an anti-inflammatory status may be a potential therapeutic strategy that can be harnessed to limit neuroinflammation and further neurodegeneration in MS. Our research has observed that the obstruction of signaling by inhibitory myelin proteins such as myelin-associated inhibitory factor, Nogo-A, with its receptor (NgR), can regulate microglial cell function and activity in pre-clinical animal studies. Our review explores the microglial role and polarization in MS pathology. Additionally, the potential therapeutics of targeting Nogo-A/NgR cellular mechanisms on microglia migration, polarization and phagocytosis for neurorepair in MS and other demyelination diseases will be discussed.
