Increased expression of ApoA1 after neuronal injury may be beneficial for healing.

ApoA1 is a player in reverse cholesterol transport that initiates multiple cellular pathways on binding to its receptor ABCA1. Its relation to neuronal injury is however unclear. We found ApoA1 to be increasingly abundant at a later time point in the secondary phase of traumatic spinal cord injury. In a cellular injury model of neuroblastoma, ApoA1 showed an initial diminished expression after infliction of injury, which sharply increased thereafter. Subsequently, ApoA1 was shown to alter wound healing dynamics in neuroblastoma injury model. It was observed that an initial lag in scratch wound closure was followed by rapid healing in the ApoA1 treatment group. Activation of ERK pathway and Actin polymerisation by ApoA1 corroborated its role in healing after neuronal injury. We propose that ApoA1 is increasingly expressed and secreted as a delayed response to neuronal injury, and this is a self-protecting mechanism of the injured system.

Possible role of apolipoprotein A1 in healing and cell death after neuronal injury.

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.

Altered levels of amyloid precursor protein intracellular domain-interacting proteins in Alzheimer disease.

BACKGROUND: The amyloid precursor protein intracellular domain (AICD) is an intrinsically unstructured molecule with functional promiscuity that plays an important role in determining the fate of the neurons during its degeneration. Its association with Alzheimer disease (AD) recently played a key role in propelling scientists to choose AICD as a major molecule of interest. Although several studies have been conducted elucidating AICD's participation in inducing neurodegenerative outcomes in AD condition, much remains to be deciphered regarding the linkage of AICD with cellular pathways in the AD scenario. RESULTS: In the present study, we have pulled down interactors of nonphosphorylated AICD from the cerebrospinal fluid of AD subjects, identified them by matrix assisted laser desorption ionization mass spectrometry, and subsequently studied the differential expression of these interactors in AD and control cases by 2-dimensional difference gel electrophoresis. The study has yielded some AICD-interactors that are differentially expressed in the AD cases and are involved in diverse cellular functions. CONCLUSIONS: This proteomic-based approach highlights the first step in finding the possible cellular pathways engaged in AD pathophysiology on the basis of interaction of one or more of their members with AICD.