Pentraxins are a superfamily of evolutionarily conserved proteins that are characterized by their multimeric architecture and their calcium-dependent binding. They can be broadly grouped into two subfamilies: short pentraxins and long pentraxins. Pentraxins regulate many processes in the brain as well as the periphery. Neuronal pentraxin 2 (NP2/NPTX2), also known as neuronal activity-regulated pentraxin (Narp), is an immediate-early gene that has been shown to play a critical role in guiding synaptic plasticity. NP2 has been previously linked to excitatory neurotransmission, based on its ability to aggregate excitatory receptors in the central nervous system. The mechanisms mediating the effects of NP2 on excitatory neurotransmission remain unclear and warrants further investigation. This review article focuses on the biological features of NP2 and discusses the literature supporting a role for NP2 and other pentraxins in glutamatergic signaling. An analysis of evidence around the role of pentraxins in neuropathology is also reviewed.
Astrocytes have been associated with the failure of axon regeneration in the central nervous system (CNS), as it undergoes reactive gliosis in response to damages to the CNS and functions as a chemical and physical barrier to axon regeneration. However, beneficial roles of astrocytes have been extensively studied in the spinal cord over the years, and a growing body of evidence now suggests that inducing astrocytes to become more growth-supportive can promote axon regeneration after spinal cord injury (SCI). In retina, astrocytes and Müller cells are known to undergo reactive gliosis after damage to retina and/or optic nerve and are hypothesized to be either detrimental or beneficial to survival and axon regeneration of retinal ganglion cells (RGCs). Whether they can be induced to become more growth-supportive after retinal and optic nerve injury has yet to be determined. In this review, we pinpoint the potential molecular pathways involved in the induction of growth-supportive astrocytes in the spinal cord and suggest that stimulating the activation of these pathways in the retina could represent a new therapeutic approach to promoting survival and axon regeneration of RGCs in retinal degenerative diseases.
The mammalian central nervous system (CNS) does not spontaneously regenerate, thereby limiting functional recovery following numerous CNS injuries. Neural repair is restricted due to both the inhibitory extracellular environment post-injury and the limited intrinsic capabilities of adult neurons. The visual system, including retinal ganglion cells (RGCs), and their axons, the optic nerve, is widely used as a model to study molecular mechanisms associated with neuroprotection and regeneration following CNS injury.Many potential therapeutic strategies have been discovered using this model with variable success in terms of promoting axon regeneration. Recent work has suggested that modulating neural activity can protect neurons and promote axon regeneration after injury; however, this area of research remains in its infancy. Activity-dependent signalling molecules, such as neuronal pentraxin 2 (NP2), have been suggested as critical modulators of neuroplasticity but have not been previously implicated in CNS neuroprotection or axon regeneration. This thesis examined the role of NP2 in protecting RGCs and promoting axon regeneration, using in vitro, ex vivo and in vivo (optic nerve injury) techniques. Given that previous work has supported the notion that RGCs lose intrinsic capacity for regeneration with age, the developmental expression pattern of NP2 was characterized. Additionally, the impact of NP2 treatment on RGC survival, using an in vitro RGC culture model, was evaluated. Furthermore, the ability of NP2 to enhance RGC neurite outgrowth using both in vitro and ex vivo model systems was examined. To assess the in vivo impact of exogenous NP2 administration on RGC survival and axon Firstly, I thank God for giving me the strength to persevere and successfully complete this chapter of my life.I would like to express my sincerest gratitude to many people for their support and encouragement throughout my studies. I would like to start by thanking and expressing my immeasurable amount of gratitude to my supervisor, Dr. Patrice D. Smith. Anytime I was uncertain how to proceed, her door was always open; she always answered every question with a smile. Her guidance and support helped me build confidence in myself and made me a better researcher. It was a privilege to work under Dr. Smith's guidance and the completion of this thesis is a testament to her endless patience and constant encouragement. I would like to thank my thesis committee members, Dr. Hayley and Dr.Hildebrand, for their time, insight into my thesis and for their continued support. I would like to express my sincere appreciation to Dr.
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