engleski

Search for the molecules underlying neuroregeneration in opossum (Monodelphis domestica)

One of the major challenges of modern neurobiology concerns the inability of the adult mammalian central nervous system (CNS) to regenerate and repair itself after injury or after neuronal loss in neurodegenerative diseases. Even though our understanding of molecular and cellular mechanisms that promote or inhibit neuronal regeneration is expanding, it is still unclear what are the key differences between the neuronal systems that can and cannot regenerate, and how they can be manipulated to revert the outcome. For reasons yet unknown, with development and age, the mammalian CNS loses its capacity for functionally relevant repair after injury, as it is observed on the evolutionary scale. A convenient model to study cellular and molecular basis of this loss is neonatal opossum (Monodelphis domestica). Opossums are marsupials that are born very immature with the unique possibility to successfully regenerate postnatal spinal cord after injury in the first two weeks of their life, after which this ability abruptly stops. In the previous studies, differentially expressed genes were identified in opossum spinal cords during the critical period of development when regeneration stops being possible, revealing the molecules involved in nucleic acid management, protein synthesis and processing, control of cell growth, structure and motility, cell signaling, extracellular matrix molecules and their receptors. The transcriptomic data were upgraded with the proteomic research, to select the overlapping molecules as the most promising candidates controlling regeneration, to be tested in functional studies. Among the genes and proteins that are differentially distributed in opossum spinal tissue that can and cannot regenerate after injury, we identified the numerous proteins related to neurodegenerative diseases, such as Huntington’s, Parkinson’s, Alzheimer's disease and ALS, as well as the transcription factors that control the activity of the neuronal stem cells, such as ATF3. The identified molecules are the good candidates for further functional regenerative studies as well as potential new therapeuthic targets.

neuroregeneration ; transcriptomics ; proteomics ; neurodegenerative diseases ; neuronal stem cells

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