Identification of astrocytic proteins of clinicalimportance in multiple sclerosis MS using CSF derived from MS patients

Abstract

Multiple sclerosis (MS) is an incurable debilitating autoimmune neurodegenerative disorder of the central nervous system (CNS) affecting young adult with no strategy for early diagnosis. The ensuing autoimmune inflammatory damage manifests in the form of demyelination, astrogliosis and damage to axons in the CNS. The neurodegenerative processes are considered to precede the demyelination. Genetic and environmental aspects contribute to very much to the development of MS. Local immune response mounted by astrocytes is a big player in the progression and pathogenesis of MS. Studies demonstrate that astrocytes respond to stress and insults by upregulating inflammatory processes and that astrocyte activation have been detected in animal models of neuronal injury such as ischemia, axotomy, and neurotoxic insult, and in the human brain in neurodegenerative diseases like Alzheimer s disease including MS. Multiple roles of astrocyte in both lesion development and repair in the MS have been reviewed. These reactive astrocytes produce a wide array of proinflammatory molecules, including nitric oxide, proinflammatory cytokines and chemokines. This aspect is elegantly shown in glia maturation factor beta (GMF-and#946;) knock out mice wherein animals failed to develop full blown experimental autoimmune encephalomyelitis (EAE) with minimal inflammatory response with practically nil clinical symptoms. However, little has been done to identify the autoimmune response to astrocytes in the pathogenesis of the disease. As cerebrospinal fluid (CSF) lay anatomically close to brain, majority of pathophysiological changes can be captured by analyzing the CSF. Although targeted approach looking for specific protein in the CSF and its role in the pathogenesis have been done, no holistic interactome approach using total CSF components and total proteins from astrocytes exploiting far western technology have been carried out using astrocytes. (abstract attached)