Neural Regeneration Research

Physiological effects of amyloid precursor protein and its derivatives on neural stem cell biology and signaling pathways involved Raquel Coronel, Charlotte Palmer, Adela Bernabeu-Zornoza, María Monteagudo, Andreea Rosca, Alberto Zambrano, Isabel Liste Neural Regeneration Research 2019 14(10):1661-1671 The pathological implication of amyloid precursor protein (APP) in Alzheimer’s disease has been widely documented due to its involvement in the generation of amyloid-β peptide. However, the physiological functions of APP are still poorly understood. APP is considered a multimodal protein due to its role in a wide variety of processes, both in the embryo and in the adult brain. Specifically, APP seems to play a key role in the proliferation, differentiation and maturation of neural stem cells. In addition, APP can be processed through two canonical processing pathways, generating different functionally active fragments: soluble APP-α, soluble APP-β, amyloid-β peptide and the APP intracellular C-terminal domain. These fragments also appear to modulate various functions in neural stem cells, including the processes of proliferation, neurogenesis, gliogenesis or cell death. However, the molecular mechanisms involved in these effects are still unclear. In this review, we summarize the physiological functions of APP and its main proteolytic derivatives in neural stem cells, as well as the possible signaling pathways that could be implicated in these effects. The knowledge of these functions and signaling pathways involved in the onset or during the development of Alzheimer’s disease is essential to advance the understanding of the pathogenesis of Alzheimer’s disease, and in the search for potential therapeutic targets.

Challenges in microRNAs' targetome prediction and validation Jesus Eduardo Rojo Arias, Volker Busskamp Neural Regeneration Research 2019 14(10):1672-1677 MicroRNAs (miRNAs) are small RNA molecules with important roles in post-transcriptional regulation of gene expression. In recent years, the predicted number of miRNAs has skyrocketed, largely as a consequence of high-throughput sequencing technologies becoming ubiquitous. This dramatic increase in miRNA candidates poses multiple challenges in terms of data deposition, curation, and validation. Although multiple databases containing miRNA annotations and targets have been developed, ensuring data quality by validating miRNA-target interactions requires the efforts of the research community. In order to generate databases containing biologically active miRNAs, it is imperative to overcome a multitude of hurdles, including restricted miRNA expression patterns, distinct miRNA biogenesis machineries, and divergent miRNA-mRNA interaction dynamics. In the present review, we discuss recent advances and limitations in miRNA prediction, identification, and validation. Lastly, we focus on the most enriched neuronal miRNA, miR-124, and its gene regulatory network in human neurons, which has been revealed using a combined computational and experimental approach.

Can we further optimize therapeutic hypothermia for hypoxic-ischemic encephalopathy? Anthony Davies, Guido Wassink, Laura Bennet, Alistair J Gunn, Joanne O Davidson Neural Regeneration Research 2019 14(10):1678-1683 Perinatal hypoxic-ischemic encephalopathy is a leading cause of neonatal death and disability. Therapeutic hypothermia significantly reduces death and major disability associated with hypoxic-ischemic encephalopathy; however, many infants still experience lifelong disabilities to movement, sensation and cognition. Clinical guidelines, based on strong clinical and preclinical evidence, recommend therapeutic hypothermia should be started within 6 hours of birth and continued for a period of 72 hours, with a target brain temperature of 33.5 ± 0.5°C for infants with moderate to severe hypoxic-ischemic encephalopathy. The clinical guidelines also recommend that infants be rewarmed at a rate of 0.5°C per hour, but this is not based on strong evidence. There are no randomized controlled trials investigating the optimal rate of rewarming after therapeutic hypothermia for infants with hypoxic-ischemic encephalopathy. Preclinical studies of rewarming are conflicting and results were confounded by treatment with sub-optimal durations of hypothermia. In this review, we evaluate the evidence for the optimal start time, duration and depth of hypothermia, and whether the rate of rewarming after treatment affects brain injury and neurological outcomes.

P2X7 receptor signaling during adult hippocampal neurogenesis Hannah C Leeson, Tailoi Chan-Ling, Michael D Lovelace, Jeremy C Brownlie, Ben J Gu, Michael W Weible Neural Regeneration Research 2019 14(10):1684-1694 Neurogenesis is a persistent and essential feature of the adult mammalian hippocampus. Granular neurons generated from resident pools of stem or progenitor cells provide a mechanism for the formation and consolidation of new memories. Regulation of hippocampal neurogenesis is complex and multifaceted, and numerous signaling pathways converge to modulate cell proliferation, apoptosis, and clearance of cellular debris, as well as synaptic integration of newborn immature neurons. The expression of functional P2X7 receptors in the central nervous system has attracted much interest and the regulatory role of this purinergic receptor during adult neurogenesis has only recently begun to be explored. P2X7 receptors are exceptionally versatile: in their canonical role they act as adenosine triphosphate-gated calcium channels and facilitate calcium-signaling cascades exerting control over the cell via calcium-encoded sensory proteins and transcription factor activation. P2X7 also mediates transmembrane pore formation to regulate cytokine release and facilitate extracellular communication, and when persistently stimulated by high extracellular adenosine triphosphate levels large P2X7 pores form, which induce apoptotic cell death through cytosolic ion dysregulation. Lastly, as a scavenger receptor P2X7 directly facilitates phagocytosis of the cellular debris that arises during neurogenesis, as well as during some disease states. Understanding how P2X7 receptors regulate the physiology of stem and progenitor cells in the adult hippocampus is an important step towards developing useful therapeutic models for regenerative medicine. This review considers the relevant aspects of adult hippocampal neurogenesis and explores how P2X7 receptor activity may influence the molecular physiology of the hippocampus, and neural stem and progenitor cells.

Gamma-aminobutyric acid (GABA) promotes recovery from spinal cord injury in lampreys: role of GABA receptors and perspective on the translation to mammals Daniel Romaus-Sanjurjo, María Celina Rodicio, Antón Barreiro-Iglesias Neural Regeneration Research 2019 14(10):1695-1696

Modulating neuronal plasticity with choline Eunice W. M. Chin, Eyleen L.K. Goh Neural Regeneration Research 2019 14(10):1697-1698

Human neural stem cell transplants to address multiple pathologies associated with traumatic brain injury Helene Clervius, Mirza Baig, Anil Mahavadi, Shyam Gajavelli Neural Regeneration Research 2019 14(10):1699-1700

Glutathione precursors shield the brain from trauma Lilia Koza, Daniel A Linseman Neural Regeneration Research 2019 14(10):1701-1702

Delayed peripheral treatment with neurotrophin-3 improves sensorimotor recovery after central nervous system injury Sotiris G Kakanos, Lawrence D.F. Moon Neural Regeneration Research 2019 14(10):1703-1704

Diterpenes and the crosstalk with the arachidonic acid pathways, relevance in neurodegeneration Juan M Zolezzi, Nibaldo C Inestrosa Neural Regeneration Research 2019 14(10):1705-1706

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com