nach oben

Neurotoxicity Research

Erschienen in:

01.10.2009

Commentary: Regulating proNGF Action: Multiple Targets for Therapeutic Intervention

verfasst von: Barbara L. Hempstead

Erschienen in: Neurotoxicity Research | Ausgabe 3/2009

Einloggen, um Zugang zu erhalten

Abstract

Neurotrophins are initially synthesized as precursor forms that are cleaved to release C-terminal mature forms that bind to Trk receptors to initiate survival and differentiative responses. Recent studies suggest that the precursor form of NGF (proNGF) acts as a distinct ligand by binding to a receptor complex of p75 and sortilin to initiate cell death. Induction of proNGF and p75 has been observed in multiple pathological states and injury models in the central nervous system, and blockade of proNGF/p75 interaction is efficacious in limiting neuronal apoptosis. Multiple strategies that may act to limit proNGF action are considered as potential therapeutic targets for future development.

Al-Shawi R, Hafner A, Olsen J, Chun S, Raxa S, Thrasivoulou C, Lovestone S, Killick R, Simons P, Cowen T (2008) Neurotoxic and neurotrophic roles of proNGF and the receptor sortilin in the adult and ageing nervous system. Eur J NeuroSci 27:2103–2114PubMedCrossRef

Althaus HH, Kloppner S (2006) Mature pig oligodendrocytes rapidly process human recombinant pro-nerve growth factor and do not undergo cell death. J Neurochem 98:506–517PubMedCrossRef

Arnett MG, Ryals JM, Wright DE (2007) pro-NGF, sortilin and p75NTR: potential mediator of injury induced apoptosis in the mouse dorsal root ganglion. Brain Res 1183:32–42PubMedCrossRef

Bamji SX, Majdan M, Pozniak CD, Belliveau DJ, Aloyz R, Kohn J, Causing CG, Miller FD (1998) The p75 neurotrophin receptor mediates neuronal apoptosis and is essential for naturally occurring sympathetic neuron death. J Cell Biol 140:911–923PubMedCrossRef

Beattie MS, Harrington AW, Lee R, Kim JY, Boyce SL, Longo FM, Bresnahan JC, Hempstead BL, Yoon SO (2002) proNGF induces p75-mediated death of oligodendrocytes following spinal cord injury. Neuron 36:375–386PubMedCrossRef

Brunello N, Reynolds M, Wrathall JR, Mocchetti I (1990) Increased nerve growth factor receptor mRNA in contused rat spinal cord. Neurosci Lett 118:238–240PubMedCrossRef

Bruno MA, Cuello AC (2006) Activity-dependent release of precursor nerve growth factor, conversion to mature nerve growth factor and its degradation by a protease cascade. Proc Natl Acad Sci USA 103:6735–6740PubMedCrossRef

Carroll SL, Schweitzer JB, Holtzman DM, Miller ML, Sclar GM, Milbrandt J (1995) Elements in the 5′ flanking sequences of the mouse low-affinity NGF receptor gene direct appropriate CNS, but not PNS, expression in transgenic mice. J Neurosci 15:3342–3356PubMed

Casaccia-Bonnefil P, Carter BD, Dobrowsky RT, Chao MV (1996) Death of oligodendrocytes mediated by the interaction of nerve growth factor with its receptor p75. Nature 383:716–719PubMedCrossRef

Chao MV (2003) Neurotrophins and their receptor: a convergence point for many signaling pathways. Nat Rev Neurosci 4:299–309PubMedCrossRef

Chen ZY, Ieraci A, Teng H, Dall H, Meng CX, Herrera DG, Nykjaer A, Hempstead BL, Lee FS (2005) Sortilin controls the intracellular sorting of brain-derived neurotrophic factor to the regulated secretory pathway. J Neurosci 25:6156–6166PubMedCrossRef

Dechant G, Barde YA (2002) The neurotrophin receptor p75(NTR): novel functions and implications for diseases of the nervous system. Nat Neurosci 5:1131–1136PubMedCrossRef

Dicou E (2008) High levels of the proNGF peptides LIP1 and LIP2 in the serum and synovial fluid of rheumatoid arthritis patients: evidence for two new cytokines. J Neuroimmunol 194:143–146PubMedCrossRef

Domeniconi M, Hempstead BL, Chao MV (2007) pro-NGF secreted by astrocytes promotes motor neuron cell death. Mol Cell Neurosci 34:271–279PubMedCrossRef

Dzwonek J, Rylski M, Kaczmarek L (2004) Matrix metalloproteinases and their endogenous inhibitors in neuronal physiology of the adult brain. FEBS Lett 567:129–135PubMedCrossRef

Fahnestock M, Michalski B, Xu B, Coughlin MD (2001) The precursor pro-nerve growth factor is the predominant form of nerve growth factor in brain and is increased in Alzheimer’s disease. Mol Cell Neurosci 18:210–220PubMedCrossRef

Frade JM, Barde YA (1998) Microglial-derived nerve growth factor causes cell death in the developing retina. Neuron 20:35–41PubMedCrossRef

Frade JM, Barde YA (1999) Genetic evidence for cell death mediated by nerve growth factor and the neurotrophin receptor p75 in the developing mouse retina and spinal cord. Development 126:683–690PubMed

Harrington AW, Leiner B, Blechschmitt C, Arevalo JC, Lee R, Morl K, Meyer M, Hempstead BL, Yoon SY, Giehl KM (2004) Secreted proNGF is a pathophysiolocial death-inducing ligand after CNS injury. Proc Natl Acad Sci USA 101:6226–6230PubMedCrossRef

He XL, Garcia KC (2004) Structure of nerve growth factor complexed with the shared neurotrophin receptor p75. Science 304:870–875PubMedCrossRef

Hempstead BL (2002) The many faces of p75NTR. Curr Opin Neurobiol 12:260–267PubMedCrossRef

Huang EJ, Reichardt LF (2001) Trk receptors: roles in neuronal signal transduction. Annu Rev Biochem 72:609–642CrossRef

Huber LJ, Chao MV (1995) Mesenchymal and neuronal cell expression of the p75 neurotrophin receptor gene occur by different mechanisms. Dev Biol 167:227–238PubMedCrossRef

Jansen P, Giehl K, Nyengaard JR, Teng K, Lioubinski O, Sjoegaard SS, Breiderhoff T, Gotthardt M, Lin F, Eilers A, Petersen CM, Lewin GR, Hempstead BL, Willnow TE, Nykjaer A (2007) Roles for the pro-neurotrophin receptor sortilin in neuronal development, aging and brain injury. Nat Neurosci 10:1449–1457PubMedCrossRef

Jaworski J, Biedermann IW, Lapinska J, Szkiarczyk A, Figiel I, Konopka D, Nowicka D, Filipkowski RK, Hetman M, Kowalczyk A, Kaczmarek L (1999) Neuronal excitation-driven and AP-1 dependent activation of tissue inhibitor of metalloproteinase-1 gene expression in rodent hippocampus. J Biol Chem 274:28106–28112PubMedCrossRef

Kenchappa RS, Zampieri N, Chao MV, Barker PA, Teng HK, Hempstead BL, Carter BD (2006) Ligand-dependent cleavage of the p75 receptor is necessary for NRIF nuclear translocation and apoptosis in sympathetic neurons. Neuron 50:219–232PubMedCrossRef

Lee R, Kermani P, Teng KK, Hempstead BL (2001) Regulation of cell survival by secreted pro-neurotrophins. Science 294:1945–1948PubMedCrossRef

Lorenzi S, Albers DS, LeWitt PA, Chirichigno JW, Hilgenberg SL, Cudkowicz ME, Beal MF (2003) Tissue inhibitors of matrix metalloproteinases are elevated in cerebrospinal fluid of neurodegenerative diseases. J Neurol Sci 207:71–76CrossRef

Lou H, Kim SK, Zaitsev E, Snell CR, Lu B, Loh YP (2005) Sorting and activity-dependent secretion of BDNF require interaction of a specific motif with the sorting receptor carboxypeptidase E. Neuron 45:245–255PubMedCrossRef

Massa SM, Xie Y, Yang T, Harrington AW, Kim ML, Yoon SO, Kraemer R, Moore LA, Hempstead BL, Longo FM (2006) Small, nonpeptide p75NTR ligands induce survival signaling and inhibit proNGF-induced death. J Neurosci 26:5230–5288CrossRef

McCormick PJ, Dumaresq-Doiron K, Pluviose AS, Pichette V, Tosato G, Lefrancois S (2008) Palmitoylation controls recycling in lyosomal sorting and trafficking. Traffic 9:1984–1997PubMedCrossRef

Mowla SJ, Pareek S, Farhadi HF, Petrecca K, Fawcett JP, Seidah NG, Morris SJ, Sossin WS, Murphy RA (1999) Differential sorting of nerve growth factor and brain-derived neurotrophic factor in hippocampal neurons. J Neurosci 19:2069–2080PubMed

Ni X, Morales CR (2006) The lysosomal trafficking of acid sphingomyelinase is mediated by sortilin and mannose 6-phosphate receptor. Traffic 7:889–902PubMedCrossRef

Nykjaer A, Lee R, Teng KK, Jansen P, Madsen P, Nielsen MS, Jacobsen C, Kliemannel M, Schwarz E, Willnow TE, Hempstead BL, Petersen CM (2004) Sortilin is essential for proNGF-induced neuronal cell death. Nature 427:843–848PubMedCrossRef

Patil N, Lacy E, Chao MV (1990) Specific neuronal expression of human NGF receptors in the basal forebrain and cerebellum of transgenic mice. Neuron 4:437–447PubMedCrossRef

Pedraza CE, Podlesniy P, Vidal N, Arevalo JC, Lee R, Hempstead BL, Ferrer I, Iglesias M, Espinet C (2005) pro-NGF isolated from the human brain affected by Alzheimer’s disease induces neuronal apoptosis mediated by p75NTR. Am J Pathol 166:533–543PubMed

Peterson S, Bogenmann E (2003) Osmotic swelling induces p75 neurotrophin receptor (p75NTR) expression via nitric oxide. J Biol Chem 278:33943–33950PubMedCrossRef

Quistgaard EM, Madsen P, Grøftehauge MK, Nissen P, Petersen CM, Thirup SS (2009) Ligands bind to Sortilin in the tunnel of a ten-bladed beta propeller domain. Nat Struct Mol Biol 16:96–98PubMedCrossRef

Ramos A, Ho WC, Forte S, Dickson K, Boutilier J, Favell K, Barker PA (2007) Hypo-omolar stress induces p75NTR expression by activating Sp1-dependent transcription. J Neurosci 27:1498–1506PubMedCrossRef

Roux PP, Barker PA (2002) Neurotrophin signaling through the p75 receptor. Prog Neurobiol 67:203–233PubMedCrossRef

Schecterson LC, Bothwell M (2008) An all-purpose tool for axon guidance. Sci Signal 1(47):pe50PubMedCrossRef

Sehgal A, Patil N, Chao M (1988) A constitutive promoter directs expression of the nerve growth factor receptor gene. Mol Cell Biol 8:3160–3167PubMed

Shetty AK, Zaman V, Shetty GA (2003) Hippocampal neurotrophin levels in a kainate model of temporal lobe epilepsy: a lack of correlation between brain-derived neurotrophic factor content and progression of aberrant dentate mossy fiber sprouting. J Neurochem 87:147–159PubMedCrossRef

Srinivasan B, Roque CH, Hempstead BL, Al-Ubaidi MR, Roque RS (2004) Microglia-derived pronerve growth factor promotes photoreceptor cell death via p75 neurotrophin receptor. J Biol Chem 279:41839–41943PubMedCrossRef

Suter U, Heymach JV Jr, Shooter EM (1991) Two conserved domains in the NGF propeptide are necessary and sufficient for the biosynthesis of correctly processed and biologically active NGF. EMBO J 10:2395–2400PubMed

Troy CM, Friedman JE, Friedman WJ (2002) Mechanisms of p75-mediated death of hippocampal neurons. Roles of caspases. J Biol Chem 277:34295–34302PubMedCrossRef

Volosin M, Trotter C, Cragnolini A, Kenchappa RS, Light M, Hempstead BL, Carter BD, Friedman WJ (2008) Induction of proneurotrophins and activation of p75NTR-mediated apoptosis via neurotrophin receptor-interacting factor in hippocampal neurons after seizures. J Neurosci 28:9870–9879PubMedCrossRef

Wei Y, Wang N, Lu Q, Zhang N, Sheng D, Li J (2007) Enhanced protein expressions of sortilin and p75NTR in retina of rat following elevated intraocular pressure induced retinal ischemia. Neurosci Lett 429:169–174PubMedCrossRef

Yang J, Siao CJ, Nagappan G, Marinic T, Jing D, McGrath K, Chen ZY, Mark W, Tessarollo L, Lee FS, Lu B, Hempstead BL (2009) Neuronal release of proBDNF. Nat Neurosci 12:113–115PubMedCrossRef

Yoon SO, Casaccia-Bonefil P, Carter BD, Chao MV (1998) Competitive signaling between TrkA and p75 nerve growth factor receptors determines cell survival. J Neurosci 18:3273–3281PubMed

Yune TY, Lee JY, Jung GY, Kim SJ, Jiang MH, Kim YM, Oh YJ, Markelonis GJ, Oh TH (2007) Minocycline alleviates death of oligodendrocytes by inhibiting pro-nerve growth factor production in microglia after spinal cord injury. J Neurosci 27:7751–7761PubMedCrossRef

Titel: Commentary: Regulating proNGF Action: Multiple Targets for Therapeutic Intervention
verfasst von: Barbara L. Hempstead
Publikationsdatum: 01.10.2009
Verlag: Springer-Verlag
Erschienen in: Neurotoxicity Research / Ausgabe 3/2009
Print ISSN: 1029-8428
Elektronische ISSN: 1476-3524
DOI: https://doi.org/10.1007/s12640-009-9054-9

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Sozialer Aufstieg verringert Demenzgefahr

24.05.2024 Demenz Nachrichten

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Was nützt die Kraniektomie bei schwerer tiefer Hirnblutung?

17.05.2024 Hirnblutung Nachrichten

Eine Studie zum Nutzen der druckentlastenden Kraniektomie nach schwerer tiefer supratentorieller Hirnblutung deutet einen Nutzen der Operation an. Für überlebende Patienten ist das dennoch nur eine bedingt gute Nachricht.

Thrombektomie auch bei großen Infarkten von Vorteil

16.05.2024 Ischämischer Schlaganfall Nachrichten

Auch ein sehr ausgedehnter ischämischer Schlaganfall scheint an sich kein Grund zu sein, von einer mechanischen Thrombektomie abzusehen. Dafür spricht die LASTE-Studie, an der Patienten und Patientinnen mit einem ASPECTS von maximal 5 beteiligt waren.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2009

IGF-1 and pAKT Signaling Promote Hippocampal CA1 Neuronal Survival Following Injury to Dentate Granule Cells

Cell Cycle Activation and CNS Injury

Role of Tat Protein in HIV Neuropathogenesis

CXCR4 and CXCL12 Expression is Increased in the Nigro-Striatal System of Parkinson’s Disease

Nitric Oxide as an Initiator of Brain Lesions During the Development of Alzheimer Disease