The Experts below are selected from a list of 7962 Experts worldwide ranked by ideXlab platform
Susan J Hayflick - One of the best experts on this subject based on the ideXlab platform.
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Chapter 19 - Neurodegeneration with brain iron accumulation
2018Co-Authors: Susan J Hayflick, Manju Ann Kurian, Penelope HogarthAbstract:Neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of disorders affecting children and adults. These rare disorders are often first suspected when increased basal ganglia iron is observed on brain magnetic resonance imaging. For the majority of NBIA disorders the genetic basis has been delineated, and clinical testing is available. The four most common NBIA disorders include pantothenate kinase-associated neurodegeneration (PKAN) due to mutations in PANK2, phospholipase A2-associated neurodegeneration caused by mutation in PLA2G6, mitochondrial membrane protein-associated neurodegeneration from mutations in C19orf12, and beta-propeller protein-associated neurodegeneration due to mutations in WDR45. The ultrarare NBIA disorders are caused by mutations in CoASY, ATP13A2, and FA2H (causing CoA synthase protein-associated neurodegeneration, Kufor-Rakeb disease, and fatty acid hydroxylase-associated neurodegeneration, respectively). Together, these genes account for disease in approximately 85% of patients diagnosed with an NBIA disorder. New NBIA genes are being recognized with increasing frequency as a result of whole-exome sequencing, which is also facilitating early ascertainment of patients whose phenotype is often nonspecific.
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novel wdr45 mutation and pathognomonic bpan imaging in a young female with mild cognitive delay
Pediatrics, 2015Co-Authors: Michelle Long, Nishard Abdeen, Penelope Hogarth, Susan J Hayflick, Michael T. Geraghty, Sunita VenkateswaranAbstract:β-propeller protein-associated neurodegeneration (BPAN) is a recently identified X-linked dominant form of neurodegeneration with brain iron accumulation caused by mutations in the WDR45 gene. BPAN commonly presents as global developmental delay in childhood with rapid onset of parkinsonism and dementia in early adulthood and associated pathognomonic changes seen on brain MRI. In this case report, we present a pediatric patient with mild cognitive delay and pathognomonic MRI changes indicative of BPAN preceding neurologic deterioration who is found to have a novel de novo mutation in the WDR45 gene.
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wdr45 mutation in atypical rett syndrome with brain iron accumulation
Movement Disorders Clinical Practice, 2015Co-Authors: Sarah J Crisp, Esther Meyer, Allison Gregory, Hayley Archer, Manju Ann Kurian, Susan J Hayflick, Rajith De SilvaAbstract:Keywords: BPAN ; Rett syndrome; WDR45; neurodegeneration with brain iron accumulation; developmental delay
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β-Propeller protein-associated neurodegeneration: a new X-linked dominant disorder with brain iron accumulation.
Brain : a journal of neurology, 2013Co-Authors: Susan J Hayflick, Michael C. Kruer, Allison Gregory, Manju Ann Kurian, Henry H Houlden, Lynn Sanford, James Anderson, Tobias B. Haack, Nathalie Boddaert, Sami I. HarikAbstract:Neurodegenerative disorders with high iron in the basal ganglia encompass an expanding collection of single gene disorders collectively known as neurodegeneration with brain iron accumulation. These disorders can largely be distinguished from one another by their associated clinical and neuroimaging features. The aim of this study was to define the phenotype that is associated with mutations in WDR45, a new causative gene for neurodegeneration with brain iron accumulation located on the X chromosome. The study subjects consisted of WDR45 mutation-positive individuals identified after screening a large international cohort of patients with idiopathic neurodegeneration with brain iron accumulation. Their records were reviewed, including longitudinal clinical, laboratory and imaging data. Twenty-three mutation-positive subjects were identified (20 females). The natural history of their disease was remarkably uniform: global developmental delay in childhood and further regression in early adulthood with progressive dystonia, parkinsonism and dementia. Common early comorbidities included seizures, spasticity and disordered sleep. The symptoms of parkinsonism improved with l-DOPA; however, nearly all patients experienced early motor fluctuations that quickly progressed to disabling dyskinesias, warranting discontinuation of l-DOPA. Brain magnetic resonance imaging showed iron in the substantia nigra and globus pallidus, with a 'halo' of T1 hyperintense signal in the substantia nigra. All patients harboured de novo mutations in WDR45, encoding a beta-propeller protein postulated to play a role in autophagy. Beta-propeller protein-associated neurodegeneration, the only X-linked disorder of neurodegeneration with brain iron accumulation, is associated with de novo mutations in WDR45 and is recognizable by a unique combination of clinical, natural history and neuroimaging features.
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Beta-propeller protein-associated neurodegeneration: a new X-linked dominant disorder with brain iron accumulation
Brain, 2013Co-Authors: Susan J Hayflick, Michael C. Kruer, Allison Gregory, Manju Ann Kurian, Henry H Houlden, Lynn Sanford, Tobias B. Haack, Nathalie Boddaert, James C. Anderson, Sami I. HarikAbstract:Neurodegenerative disorders with high iron in the basal ganglia encompass an expanding collection of single gene disorders collectively known as neurodegeneration with brain iron accumulation. These disorders can largely be distinguished from one another by their associated clinical and neuroimaging features. The aim of this study was to define the phenotype that is associated with mutations in WDR45, a new causative gene for neurodegeneration with brain iron accumulation located on the X chromosome. The study subjects consisted of WDR45 mutation-positive individuals identified after screening a large international cohort of patients with idiopathic neurodegeneration with brain iron accumulation. Their records were reviewed, including longitudinal clinical, laboratory and imaging data. Twenty-three mutation-positive subjects were identified (20 females). The natural history of their disease was remarkably uniform: global developmental delay in childhood and further regression in early adulthood with progressive dystonia, parkinsonism and dementia. Common early comorbidities included seizures, spasticity and disordered sleep. The symptoms of parkinsonism improved with l-DOPA; however, nearly all patients experienced early motor fluctuations that quickly progressed to disabling dyskinesias, warranting discontinuation of l-DOPA. Brain magnetic resonance imaging showed iron in the substantia nigra and globus pallidus, with a ‘halo’ of T1 hyperintense signal in the substantia nigra. All patients harboured de novo mutations in WDR45, encoding a beta-propeller protein postulated to play a role in autophagy. Beta-propeller protein-associated neurodegeneration, the only X-linked disorder of neurodegeneration with brain iron accumulation, is associated with de novo mutations in WDR45 and is recognizable by a unique combination of clinical, natural history and neuroimaging features.
Manju Ann Kurian - One of the best experts on this subject based on the ideXlab platform.
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Chapter 19 - Neurodegeneration with brain iron accumulation
2018Co-Authors: Susan J Hayflick, Manju Ann Kurian, Penelope HogarthAbstract:Neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of disorders affecting children and adults. These rare disorders are often first suspected when increased basal ganglia iron is observed on brain magnetic resonance imaging. For the majority of NBIA disorders the genetic basis has been delineated, and clinical testing is available. The four most common NBIA disorders include pantothenate kinase-associated neurodegeneration (PKAN) due to mutations in PANK2, phospholipase A2-associated neurodegeneration caused by mutation in PLA2G6, mitochondrial membrane protein-associated neurodegeneration from mutations in C19orf12, and beta-propeller protein-associated neurodegeneration due to mutations in WDR45. The ultrarare NBIA disorders are caused by mutations in CoASY, ATP13A2, and FA2H (causing CoA synthase protein-associated neurodegeneration, Kufor-Rakeb disease, and fatty acid hydroxylase-associated neurodegeneration, respectively). Together, these genes account for disease in approximately 85% of patients diagnosed with an NBIA disorder. New NBIA genes are being recognized with increasing frequency as a result of whole-exome sequencing, which is also facilitating early ascertainment of patients whose phenotype is often nonspecific.
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wdr45 mutation in atypical rett syndrome with brain iron accumulation
Movement Disorders Clinical Practice, 2015Co-Authors: Sarah J Crisp, Esther Meyer, Allison Gregory, Hayley Archer, Manju Ann Kurian, Susan J Hayflick, Rajith De SilvaAbstract:Keywords: BPAN ; Rett syndrome; WDR45; neurodegeneration with brain iron accumulation; developmental delay
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β-Propeller protein-associated neurodegeneration: a new X-linked dominant disorder with brain iron accumulation.
Brain : a journal of neurology, 2013Co-Authors: Susan J Hayflick, Michael C. Kruer, Allison Gregory, Manju Ann Kurian, Henry H Houlden, Lynn Sanford, James Anderson, Tobias B. Haack, Nathalie Boddaert, Sami I. HarikAbstract:Neurodegenerative disorders with high iron in the basal ganglia encompass an expanding collection of single gene disorders collectively known as neurodegeneration with brain iron accumulation. These disorders can largely be distinguished from one another by their associated clinical and neuroimaging features. The aim of this study was to define the phenotype that is associated with mutations in WDR45, a new causative gene for neurodegeneration with brain iron accumulation located on the X chromosome. The study subjects consisted of WDR45 mutation-positive individuals identified after screening a large international cohort of patients with idiopathic neurodegeneration with brain iron accumulation. Their records were reviewed, including longitudinal clinical, laboratory and imaging data. Twenty-three mutation-positive subjects were identified (20 females). The natural history of their disease was remarkably uniform: global developmental delay in childhood and further regression in early adulthood with progressive dystonia, parkinsonism and dementia. Common early comorbidities included seizures, spasticity and disordered sleep. The symptoms of parkinsonism improved with l-DOPA; however, nearly all patients experienced early motor fluctuations that quickly progressed to disabling dyskinesias, warranting discontinuation of l-DOPA. Brain magnetic resonance imaging showed iron in the substantia nigra and globus pallidus, with a 'halo' of T1 hyperintense signal in the substantia nigra. All patients harboured de novo mutations in WDR45, encoding a beta-propeller protein postulated to play a role in autophagy. Beta-propeller protein-associated neurodegeneration, the only X-linked disorder of neurodegeneration with brain iron accumulation, is associated with de novo mutations in WDR45 and is recognizable by a unique combination of clinical, natural history and neuroimaging features.
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Beta-propeller protein-associated neurodegeneration: a new X-linked dominant disorder with brain iron accumulation
Brain, 2013Co-Authors: Susan J Hayflick, Michael C. Kruer, Allison Gregory, Manju Ann Kurian, Henry H Houlden, Lynn Sanford, Tobias B. Haack, Nathalie Boddaert, James C. Anderson, Sami I. HarikAbstract:Neurodegenerative disorders with high iron in the basal ganglia encompass an expanding collection of single gene disorders collectively known as neurodegeneration with brain iron accumulation. These disorders can largely be distinguished from one another by their associated clinical and neuroimaging features. The aim of this study was to define the phenotype that is associated with mutations in WDR45, a new causative gene for neurodegeneration with brain iron accumulation located on the X chromosome. The study subjects consisted of WDR45 mutation-positive individuals identified after screening a large international cohort of patients with idiopathic neurodegeneration with brain iron accumulation. Their records were reviewed, including longitudinal clinical, laboratory and imaging data. Twenty-three mutation-positive subjects were identified (20 females). The natural history of their disease was remarkably uniform: global developmental delay in childhood and further regression in early adulthood with progressive dystonia, parkinsonism and dementia. Common early comorbidities included seizures, spasticity and disordered sleep. The symptoms of parkinsonism improved with l-DOPA; however, nearly all patients experienced early motor fluctuations that quickly progressed to disabling dyskinesias, warranting discontinuation of l-DOPA. Brain magnetic resonance imaging showed iron in the substantia nigra and globus pallidus, with a ‘halo’ of T1 hyperintense signal in the substantia nigra. All patients harboured de novo mutations in WDR45, encoding a beta-propeller protein postulated to play a role in autophagy. Beta-propeller protein-associated neurodegeneration, the only X-linked disorder of neurodegeneration with brain iron accumulation, is associated with de novo mutations in WDR45 and is recognizable by a unique combination of clinical, natural history and neuroimaging features.
Laura Ballerini - One of the best experts on this subject based on the ideXlab platform.
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carbon nanotubes in Neuroregeneration and repair
Advanced Drug Delivery Reviews, 2013Co-Authors: Alessandra Fabbro, Maurizio Prato, Laura BalleriniAbstract:In the last decade, we have experienced an increasing interest and an improved understanding of the application of nanotechnology to the nervous system. The aim of such studies is that of developing future strategies for tissue repair to promote functional recovery after brain damage. In this framework, carbon nanotube based technologies are emerging as particularly innovative tools due to the outstanding physical properties of these nanomaterials together with their recently documented ability to interface neuronal circuits, synapses and membranes. This review will discuss the state of the art in carbon nanotube technology applied to the development of devices able to drive nerve tissue repair; we will highlight the most exciting findings addressing the impact of carbon nanotubes in nerve tissue engineering, focusing in particular on neuronal differentiation, growth and network reconstruction.
Hari Shanker Sharma - One of the best experts on this subject based on the ideXlab platform.
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New perspectives on molecular and cellular mechanisms of neuroprotection and Neuroregeneration: part I
Expert Review of Neurotherapeutics, 2020Co-Authors: Hari Shanker Sharma, Aruna SharmaAbstract:Recent developments in the rapidly advancing area of neuroprotection and Neuroregeneration necessitated the need to gather over 50 of the world’s leading experts under the umbrella of the Global College of Neuroprotection and Neuroregeneration (GCNN) in its 7th Annual Meeting in Stockholm, Sweden. In this meeting, top policy-makers, together with world leaders in pharmaceutical industries, discussed the urgent need to develop new pharmaceuticals, as well as using a combination of existing ones, to treat CNS disorders in order to improve the current status of healthcare. In addition, nanobiotechnologists proposed the use of a new formulation of drugs using nanotechnologies for enhanced drug delivery to the brain for better therapeutic efficacy of the neuroprotective agents. The deliberations in this meeting provide new perspectives on the molecular and cellular mechanisms of neuroprotection and Neuroregeneration that could be utilized to improve the existing healthcare for the benefit of mankind.
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New perspectives on molecular and cellular mechanisms of neuroprotection and Neuroregeneration: part II.
Expert review of neurotherapeutics, 2020Co-Authors: Hari Shanker Sharma, Aruna SharmaAbstract:Recent developments in the rapidly advancing area of neuroprotection and Neuroregeneration necessitated the need to gather over 50 of the world's leading experts under the umbrella of the Global College of Neuroprotection and Neuroregeneration in its 7th Annual Meeting in Stockholm, Sweden. In this meeting, top policy-makers, together with world leaders in pharmaceutical industries, discussed the urgent need to develop new pharmaceuticals, as well as using a combination of existing ones, to treat CNS disorders in order to improve the current status of healthcare. In addition, nanobiotechnologists proposed the use of a new formulation of drugs using nanotechnologies for enhanced drug delivery to the brain for better therapeutic efficacy of the neuroprotective agents. The deliberations in this meeting provide new perspectives on the molecular and cellular mechanisms of neuroprotection and Neuroregeneration that could be utilized to improve the existing healthcare for the benefit of mankind.
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6th Global College of Neuroprotection and Neuroregeneration, annual meeting.
Expert Review of Neurotherapeutics, 2020Co-Authors: Hari Shanker Sharma, Aruna SharmaAbstract:The 6th Global College of Neuroprotection and Neuroregeneration (GCNN) and 5th Society for Study on Neuroplasticity and Neuroregeneration (SSNN) conference was held jointly in the Hilton Hotel, Vienna, Austria, 1–4 March 2009. This was the second annual joint conference of the two societies and it was highly successful from a scientific point of view, as it saw a gathering of the top basic and clinical scientists whose research is currently at the cutting edge of neuroscience. This conference saw 86 invited lectures from carefully selected leading scientists from around the world, along with 56 posters of young scientists researching of a focal theme. Over the 3 days, in 32 sessions, new developments in neuroprotection and new ways to enhance Neuroregeneration were discussed intensively among more than 600 delegates. In addition, approximately 40 representatives of drug companies, five representatives from scientific publishers and 14 representatives from scientific instruments and supplies-related indust...
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blood central nervous system barriers the gateway to neurodegeneration neuroprotection and Neuroregeneration chapter 17
2009Co-Authors: Hari Shanker SharmaAbstract:The microenvironment of the central nervous system (CNS) is precisely and meticulously maintained by a set of dynamic physiological barriers located within the cerebral microvessels of the brain (blood–brain barrier, BBB) and the spinal cord (blood–spinal cord barrier, BSCB), as well as within the epithelial cells of the choroid plexus separating the blood and cerebrospinal fluid (CSF) interface (blood–CSF barrier, BCSFB). The physicochemical properties of these cellular barriers are quite comparable to that of an extended plasma membrane. The BBB and the BSCB are quite tight to small molecules (12 A, Lanthanum ion), whereas BCSFB is less restrictive in nature. On the other hand, the ependymal cell linings of the cerebral ventricles and spinal canal referred to as CSF–brain barrier do not normally restrict passage of several molecules of small sizes. However, protein transport across these blood–CNS barriers (BCNSB) is severely restricted. Entry of proteins into the CNS microenvironment induces vasogenic edema formation that is primarily responsible for cell and tissue injury. These BCNSB are often compromised under a wide variety of psychological, traumatic, metabolic, ischemic, environmental, or chemical insults leading to neuronal, glial, and axonal damage. Opening of the BCSNB to various endogenous or exogenous substances and proteins alters the molecular, cellular, biochemical, immunological, and metabolic environment of the CNS leading to abnormal neuronal function and/or brain pathology. This review is focused on current status of the BCSNB breakdown in experimental models of emotional stress, traumatic injuries, psychostimulants as well as key environmental health hazards, i.e., nanoparticles and heat exposure. Breakdown of the BCNSB in these conditions altered gene expression and induced brain pathology leading to neurodegeneration. Attenuation of the BCNSB disruption with drugs or antibodies affecting neurochemical metabolism and/or neurotrophic factors markedly reduced the development of brain pathology. Taken together, these novel observations strongly point out the role of BCNSB as a “gateway” to the neurodegeneration, neuroprotection, and/or Neuroregeneration in neurological diseases.
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neurodegeneration and Neuroregeneration recent advancements and future perspectives
Current Pharmaceutical Design, 2007Co-Authors: Hari Shanker SharmaAbstract:Neuroprotection: Non-Neural Cells Regulate Neuronal Functions The term “Neuroprotection” normally denotes rescue of nerve cells. However, the non-neural cells, i.e., glial cells and endothelial cells are equally important for brain function in normal and in pathological conditions [1,2]. The number of glial cells and endothelial cells far exceeds the number of neural cells in the CNS [2,3]. In spite of this fact, most attention is still focused to rescue nerve cells following CNS injuries and the role of non-neural cells in neurodegeneration or neuroprotection is largely ignored. Thus, the term “neuroprotection” is normally misleading as neurons are in the minority in the CNS and their function depends on the survival of non-neural cells and vice versa. To restore the normal function of the CNS by pharmacological manipulation, revival of glial cells and endothelial cell functions are equally important [4-6]. The nerve cell function is largely dependent on the normal endothelial cell and glial function. Thus, it is imperative that in pathological conditions, reducing damage to endothelial cells and/or glial cells by pharmacological agents will improve nerve cell function. Alternatively, glial cells, endothelial cells are all working to maintain and regulate neuronal function in health and disease [7,8]. Taken together, it appears that both the neural and non-neural components of the CNS are working in synergy for maintaining normal brain function and alterations in any neural or non-neural component will have severe impact on CNS structure and function. Blood-Brain vs. Brain Blood Barriers Our CNS is well equipped with the blood-brain barrier that is anatomically located within the endothelial cells of the brain microvasculature [1]. It is assumed that both the luminal and the abluminal cell membranes of the endothelium are equally “tight” to maintain an effective barrier between blood to brain and brain to blood [1,2]. Interestingly, the endothelial cell function and membrane transport from brain to blood (brain-blood barrier) in relation to neurodegeneration and neurorepair mechanisms are still largely ignored [see7,8]. Thus, it is still unclear whether luminal barrier disruption always accompanied with identical damage to the abluminal barrier function. However, there are reasons to believe that when luminal membrane is permeable, the abluminal side is also showing some alteration in the membrane function. A direct evidence to support or reject this hypothesis is still lacking. Studies carried out in our laboratory suggest that hyperthermia induced breakdown of the blood-brain barrier is also associated with a leaky brain blood-barrier [5,9]. Thus, serotonin transport occurs from brain to the blood causing a massive accumulation of the amine in the circulation leading to a generalized and widespread disruption of the blood-brain barrier [9]. This large increase in plasma serotonin is largely prevented by destruction of the serotoninergic neurons into the brain [see 5,9]. This treatment did not allow brain serotonin to increase and thus, the plasma serotonin concentration is much lower resulting in a minor breakdown of the blood-brain barrier in hyperthermia [5]. This suggests that various endogenous substances, e.g., cytokines, growth factors, growth hormone etc. are released from brain in extra quantity following injury that could be transported into the blood stream to have a generalized effect on the cerebral circulation and/or brain function. However, this is entirely a new subject and requires additional investigation in details to achieve better neuroprotection in future. In this volume, the term “Neuroprotection” is employed in its widest sense to include protection of all the “neural” and “nonneural” components of the CNS. This issue highlights the role of non-neural cells; especially the function of endothelial cells and its surrounding glial cells in neurodegeneration and repair process.......
Geoffrey Burnstock - One of the best experts on this subject based on the ideXlab platform.
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an introduction to the roles of purinergic signalling in neurodegeneration neuroprotection and Neuroregeneration
Neuropharmacology, 2016Co-Authors: Geoffrey BurnstockAbstract:Purinergic signalling appears to play important roles in neurodegeneration, neuroprotection and Neuroregeneration. Initially there is a brief summary of the background of purinergic signalling, including release of purines and pyrimidines from neural and non-neural cells and their ectoenzymatic degradation, and the current characterisation of P1 (adenosine), and P2X (ion channel) and P2Y (G protein-coupled) nucleotide receptor subtypes. There is also coverage of the localization and roles of purinoceptors in the healthy central nervous system. The focus is then on the roles of purinergic signalling in trauma, ischaemia, stroke and in neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntington's diseases, as well as multiple sclerosis and amyotrophic lateral sclerosis. Neuroprotective mechanisms involving purinergic signalling are considered and its involvement in Neuroregeneration, including the role of adult neural stem/progenitor cells. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'.
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purinergic signalling in Neuroregeneration
Neural Regeneration Research, 2015Co-Authors: Geoffrey BurnstockAbstract:Purinergic signalling, adenosine 5′-triphosphate (ATP) as an extracellular signalling molecule, was proposed in 1972 (Burnstock, 1972). However, it was not generally accepted until the early 1990s when receptors for ATP and its breakdown product adenosine were cloned and characterised (Ralevic and Burnstock, 1998). Four P1 (adenosine) receptors are recognised (A1, A2A, A2B and A3), seven P2X ion channel receptors (P2X1-7) and eight P2Y G protein-coupled receptors (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, P2Y14). The purinergic signalling field is now widely accepted and expanding in many different directions (Burnstock, 2012). Purinergic signalling plays important roles in neurodegeneration, neuroprotection and Neuroregeneration (Burnstock, 2015). Trauma, ischaemia and stroke result in release of ATP/adenosine from cells in the central nervous system (CNS), which can either enhance neuronal and glial cell damage or serve as neuroprotectors. Injury produces upregulation of both P2X and P2Y receptor expression, as well as ecto-nucleotidase activity. P2X7 receptors, expressed by both neurons and glia, are activated during trauma and inflammation, leading to neurodegeneration. P2X7 receptors are also involved in neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's disease, multiple sclerosis and amyotrophic lateral sclerosis (Burnstock, 2008). P2X7 receptor antagonists are claimed to be neuroprotective. P1 and P2Y1 receptors also participate in neuroprotective mechanisms. A2A receptor antagonists are being explored for the treatment of Parkinson's disease and P2Y-like GPR17 antagonists are promising for the treatment of multiple sclerosis. ATP and its analogues are involved in tissue remodelling in response to injury and play a role in regulation of repair and regeneration (Burnstock and Verkhratsky, 2010). The weak regenerative capacity of injured neurons is an obstacle for neural repair, although the neonatal brain has a greater capacity for recovery than the adult brain. Purinergic drugs have been used to promote regeneration of injured and degenerating nerves in the brain and spinal cord. A signalling molecule, protein kinase B/Akt, regulates cell survival, growth and metabolism and inhibits apoptosis, and traumatic brain injury activates Akt. When cortical astrocytes were subjected to trauma or mechanical strain, ATP was released and there was Akt activation. PPADS, a P2 receptor antagonist, attenuated the Akt activation. Trauma-induced activation of purinergic signalling in astrocytes via P2Y4 receptors stimulates the synthesis and release of thrombospondin-1, an extracellular matrix molecule that induces synapse formation during development. This may play a role in CNS repair and remodelling after injury. Astrogliosis, the response of astrocytes to brain damage, is characterised by cell proliferation and remodelling of the neural circuitry. Astrogliosis is triggered by stimulation of purinoceptors in the CNS. Growth factors such as fibroblast growth factor, epidermal growth factor and platelet-derived growth factor combined with ATP can stimulate astrocyte proliferation, contributing to the process of reactive astrogliosis. P2Y receptors mediate reactive astrogliosis via induction of cyclo-oxygenase-2, and P2Y receptor antagonists reduce astrogliosis. Reactive astrogliosis limits brain damage, as well as promoting post-insult remodelling and recovery of neural function. Activation of P2Y2 receptors can promote regeneration of nerves and glial cells in damaged brain (see Arthur et al., 2005). The P2Y-like GPR17 is a sensor of damage of the CNS, which participates in lesion repair in the rodent brain and in patients with traumatic brain injury (Franke et al., 2013). When enteric nerve plexus was transplanted into the striatum of the brain, there was sprouting of central neurons (Tew et al., 1992) and synergistic actions of growth factors and ATP had been recognized in 1989 and evidence was presented to suggest that a growth factor releazed from enteric glial cells acted synergistically with ATP (and its breakdown product, adenosine) and nitric oxide. A similar synergistic activity of purines and growth factors may be involved in stem cell activity (Burnstock and Ulrich, 2011). Neural stem (progenitor) cells are involved in the development of the CNS and adult neural progenitor cells are involved in regeneration following injury (see Ulrich et al., 2012). Stem cell activation and the integration of newly formed neurons are involved in Neuroregeneration in the diseased brain (Delic and Zimmermann, 2010). Pluripotent neural precursor cells derived from primary neural stem cells proliferate to form neurons, astrocytes and oligodendrocytes, while microglia are derived from immune-like cells. ATP is one of the factors causing proliferation of human neural stem cells. Adult neural progenitor cells in the mouse subventricular zone express functional P2X4 and P2X7 receptors. P2X7 receptor agonists and antagonists may provide novel tools for regeneration therapy in neurodegenerative diseases. Neural stem cells are present in the subventricular zone of the lateral ventricle and the subgranular zone of the hippocampal dentate gyrus in adult brains and neurogenesis continues throughout life. Proliferation of rapidly dividing stem cells in the subventricular region is promoted via P2Y1 receptors. Conclusion: There is growing evidence that purinergic signalling is involved in Neuroregeneration, and drugs acting on purinoceptors are being explored to enhance regeneration. Activation of P2Y2 receptors has been claimed to promote regeneration of nerves and glial cells and activation of the P2Y-like GPR17 receptor promotes regeneration of oligodendrocytes. Neural stem cell activation is involved in Neuroregeneration and proliferation of neural stem cells involves ATP, probably acting via P2X4 and P2X7 receptors. However, the field is in its infancy and more studies are needed to establish the precise roles of purinoceptor subtype activation and antagonism in Neuroregeneration.