460 [Frontiers in Bioscience, Elite, 8, 460-477, June 1, 2016] 1. ABSTRACT Limited axonal regeneration after traumatic injuries to the CNS presents a challenge in neuroscience. Investigation of CSF from subjects with spinal cord injury (SCI) has found that the lipid catabolism pathway is implicated in the post injury scenario. Sequestration of the CNS by the blood brain barrier ensures a mechanism of cholesterol metabolism and recycling distinct from that in the peripheral tissues. Apolipoprotein A1, the protein component of high density lipoprotein (HDL), is an abundant protein in the mammalian cerebrospinal fluid. Interaction of ApoA1 with its cellular receptor, ABCA1, gives rise to several signaling events, such as the activation of Cdc42 protein leading to actin polymerisation. Emerging evidences suggest that ApoA1 mediates anti-inflammatory effects and conversely, is negatively regulated by inflammatory cytokines. Collating these findings, added to the clinical evidences of using HDL as a therapeutic target for cardio vascular diseases, we hypothesize that ApoA1 could be useful in neurite outgrowth after mechanical injury by 1) mediating polymerisation of actin and 2) restricting inflammatory responses after injury which are deleterious to healing. 2. INTRODUCTION Mechanical injuries to the central nervous system (CNS) cause irreversible tissue damage. Possible role of apolipoprotein A1 in healing and cell death after neuronal injury Mohor B. Sengupta 1 , Debashis Mukhopadhyay 1 1 Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF, Bidhannagar, Kolkata 700064, West Bengal, India TABLE OF CONTENTS 1. Abstract 2. Introduction 3. ApoA1 and HDL in the central nervous system 3.1. Structure of ApoA1 in lipid free state and in association with HDL 3.2. Basic path taken by HDL in a turnover cycle 3.3. Lipid metabolism in the central nervous system 4. Relationship of ApoA1 with inflammation 4.1. HDL in innate and adaptive immunity 4.2. ApoA1/HDL mediated disruption of lipid raft microdomains 4.3. Modulation of HDL composition during acute phase 4.4. ApoA1 and inflammatory cytokines: a vicious cycle 5. Signaling events triggered by ApoA1-ABCA1 interaction 5.1. PKA, PKC, JAK-2, MAPK and Ca 2+ pathways in cholesterol efflux 5.2. Cdc42 activation in lipid efflux 6. Can ApoA1 be a mediator in neuronal healing? 7. Concluding remarks in brief 8. Acknowledgements 9. References Because the adult (CNS) is incapable of regenerating, partial or complete loss of sensory and/or motor functions prevails after brain and spinal cord trauma. Molecular events after brain injury may differ from that of the spinal cord but both injuries cause immediate and delayed cell death (1). A plethora of molecular perturbations follow neuronal injury, the most common of which are, immune response (2), glutamate excitotoxicity (3, 4), electrolyte imbalance (5), mitochondrial damage (6, 7), lipid peroxidation by reactive oxygen (8) and nitrogen species (9), demyelination (10), apoptosis (11), which is usually triggered by inflammatory responses, cytokine release, free radicals and excitotoxicity (12) and derangements of the vascular system (13). Our understanding of the limited regeneration of functional neural connections after CNS injury is based on two specific and critical events after injury: inflammatory responses and exposure of neuritis to growth inhibitory molecules. Let us explore each of these briefly. After CNS injury, microglia, the macrophage of CNS produce inflammatory cytokines such as inteleukin-1β (IL-1β) and tumour necrosis factor α (TNF-α) (14-16). These cytokines are the major inflammatory mediators responsible for leucocyte recruitment at the site of injury. Because the brain and the spinal cord are different