Recent Advances in NGF and Related Molecules: The Continuum of the NGF “Saga”

302 Pages·2021·8.772 MB·English

by  Laura Calzà, Luigi Aloe, Luciana Giardino

Advances in Experimental Medicine and Biology 1331
Cellular Neuroscience, Neural Circuits and Systems Neuroscience
Laura Calzà
Luigi Aloe
Luciana Giardino Editors
Recent Advances
in NGF and Related
Molecules
The Continuum of the NGF “Saga”
Advances in Experimental Medicine
and Biology
Cellular Neuroscience, Neural Circuits
and Systems Neuroscience
Volume 1331
SeriesEditors
AdalbertoMerighi,DepartmentofVeterinarySciences,UniversityofTurin,
Grugliasco,Italy
LauraLossi,DepartmentofVeterinaryScience,UniversityofTurin,
Grugliasco,Italy
AlbertoGranato,DepartmentofPsychology,CatholicUniversity,Milan,Italy
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Laura Calzà Luigi Aloe
Luciana Giardino
Editors
Recent Advances in NGF
and Related Molecules
“ ”
The Continuum of the NGF Saga
Editors
LauraCalzà LuigiAloe
UniversityofBologna IRETFoundation
Ozzanodell’Emilia,Bologna,Italy Ozzanodell’Emilia,Bologna,Italy
LucianaGiardino
UniversityofBologna
Ozzanodell’Emilia,Bologna,Italy
ISSN0065-2598 ISSN2214-8019 (electronic)
AdvancesinExperimentalMedicineandBiology
ISSN2524-6577 ISSN2524-6585 (electronic)
CellularNeuroscience,NeuralCircuitsandSystemsNeuroscience
ISBN978-3-030-74045-0 ISBN978-3-030-74046-7 (eBook)
https://doi.org/10.1007/978-3-030-74046-7
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Preface: Rita Levi-Montalcini
Rita Levi-Montalcini received her medical degree and specialization in neu-
rologyandpsychiatryin1936fromtheFacultyofMedicineattheUniversity
of Turin, Italy. She then entered the Institute of Anatomy as a postgraduate
studentinthelaboratoryofGiuseppeLevi,awell-knownanatomistandtutor
oftwoother futurewinnersoftheNobelPrize inPhysiology orMedicine—
SalvatoreLuria(whowonin1969)andRenatoDulbecco(whowonin1975).
Duringherearlypostgraduatestudies,Levi-Montalciniinvestigatedtherela-
tionshipbetweenthedevelopingcentralnervoussystem(CNS)anditsperiph-
eraltargets,theresultsofwhichledhertosuggestthatthefailureofneuronsto
thrive in the absence of peripheral target tissues was due to a degenerative
process, rather than a failure of differentiation as had previously been
hypothesized by Victor Hamburger, a renowned embryologist and develop-
mentalneuroscientist.
TheNGFstorybeganin1949whenHamburgershowedLevi-Montalcini
the results achieved by one of his postgraduate students, Elmer Bueker.
Bueker had observed that implantation of a small fragment of malignant
mousetumorintothebodywallof3-daychickembryoscausedsensoryfibers
to invade the tumor. Bueker hypothesized that this effect was due to the
rapidly expanding tumor allowing the sensory fibers to branch into the
muchlargerfieldofferedbytheneoplasticcellswhichreplacedtheembryonic
tissue, a hypothesis which did not convince Rita Levi-Montalcini, who
decidedtostudytheeffectmoreextensively.Theresultsofherreinvestigation
ledLevi-Montalcinitothehypothesisthatthemousesarcomatissues180and
37, when transplanted into a chick embryo, produce and release a diffusible
agent which stimulates the growth and differentiation of developing nerve
cells. Using a variety of in vitro methodologies, she then demonstrated that
thesetumortissues produceandreleaseamoleculeabletostimulateneuritis
outgrowthfromsensoryandsympatheticnervecells,andin1952,shenamed
thismoleculenervegrowthfactor(NGF).
IncollaborationwithStanleyCohen,co-winneroftheNobelPrizein1986,
she discovered that NGF is stored in snake venom and in the submaxillary
salivaryglandofmice.
During the early 1950s, Levi-Montalcini—then Professor at the Depart-
ment of Zoology at the Washington University of St. Louis—intensified her
in vivo and in vitro studies of NGF on small rodents, while two other
scientists—first Stanley Cohen and later P. U. Angeletti—investigated the
v
vi Preface:RitaLevi-Montalcini
chemicalandbiochemicalpropertiesofNGF,bothdevisingamethodologyof
purifyinglargequantitiesofNGFfromsnakevenomandfrommousesalivary
glands.TheavailabilityoflargeamountsofNGFintheseglandsprovidedan
additionalopportunitytocarryoutnumerousandcollaborativeinvivostudies
andtoinvestigatethestructural,biochemical,andpharmacologicalactionof
NGF on sympathetic and sensory nerve cells, as well as permitting the
production of anti-NGF antibodies, and to further characterize the effects of
NGF on the development of the peripheral nervous system by injecting this
antibody into newborn rodents. The immune deprivation of NGF via the
exogenousadministrationofNGFantibodiestotheserodents,andtheobser-
vation that inhibition of circulating NGF levels results in the death of
NGF-target cells, described in the late 1960s, became known as
immunosympathectomy.
In addition to this continued scientific activity, Levi-Montalcini wrote
several books. The first, In Praise of Imperfection, is an inspiring autobio-
graphical work where she tells of her success, but also of the delays and
distractions affecting researchers, the potential mistakes they can make, and
their tendency to underestimate difficulties. A second volume entitled Il tuo
futuro (“Your future”) is dedicated to young people who during their early
lives often face the need to make vital choices, while her third book, Senza
Olio e contro Vento (“Out of oil and against the wind”), contains ten true
storiesofwell-knownandeverydaypeople,unitedbythecourageandhonesty
they showed at very difficult times of their lives. In her most recent book
L’assonellamanicaabrandelli(“Theaceupatatteredsleeve”),shediscusses
the skills and creativity of famous elderly people, and how to maintain and
improve cognitive abilities in later life. From a scientific point of view,
however,hermostimportantbookisperhapstheTheNGFSaga.
More recently, basic preclinical studies have indicated that purified NGF
has potential clinical application in ocular disorders, such as corneal ulcers,
neurotrophickeratitis,maculopathy,glaucoma,andcutaneousulcerssuchas
diabeticandrheumatoidulcersandpressuresores.
The articles published in this issue are part of a scientific contribution
presented and discussed at the Second International NGF scientific meeting
dedicatedtoRitaLevi-Montalcini,heldinBolognaonJune13–14,2019,and
organizedbyLauraCalzà,LuigiAloe,andLucianaGiardino.Amajoraimof
thisinternationalNGFmeetingwastobringattendeesuptodateonthepast,
recent, and ongoing studies in the field of the Italian Nobel Laureate in
Physiology or Medicine who discovered the first neurotrophic factor,
providing neurologists with a powerful tool for investigating the growth,
differentiation, and plasticity of nerve cells, as well as paving the way for
the identification of other specific growth factors for other cell types. As
progressisachievedbymovingcontinuouslyforwardtowardfurtherscientific
knowledge,wewerehappythattheinvitedspeakerspresentedanddiscussed
the most recent findings in the field of NGF and other neurotrophic factors,
including the recently discovered recombinant human NGF with clinical
applications for certain human ocular diseases. It is a great pity that Rita
Levi-Montalciniisnolongerwithus,asshewasatourfirstInternationalNGF
meetingheldinModenain2002.Finally,weoweadebtofgratitudetoallthe
Preface:RitaLevi-Montalcini vii
participantswhocontributedtothesuccessoftheNGFmeetingconferencein
Bologna, to the financial support provided by the IRET Foundation in
Ozzano, Bologna, and to the professional collaboration of all logistical
IRETstaff.Thismeetingwasalsopartofthe“ItalianRegenerativeMedicine
Infrastructure—IRMI” project training program (MIUR,
CTN01_00177_888744toLC).
Bologna,Italy LauraCalzà
LuigiAloe
LucianaGiardino
Contents
PartI BasicScience
1 NerveGrowthFactor:TheFirstMoleculeofthe
NeurotrophinFamily. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
LucaLorenzini,VitoAntonioBaldassarro,AgneseStanzani,
andLucianaGiardino
2 TheFirstandLastTimeIMetRitaLevi-Montalcini:
FromtheInsectNeurotrophicFactortotheNerveGrowth
FactorClinicalApplication. . . . . . . . . . . . . . . . . . . . . . . . . . 11
LuigiAloe
3 NGFSignalinginEndosomes. . . . . . . . . . . . . . . . . . . . . . . . . 19
NaoyaYamashita
4 TheNGFMetabolicPathway:NewOpportunitiesfor
BiomarkerResearchandDrugTargetDiscovery. . . . . . . . . . 31
RowanPentzandM.FlorenciaIulita
PartII DevelopmentandRegeneration
5 NGFandEndogenousRegeneration:FromEmbryology
TowardTherapies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
VitoAntonioBaldassarro,LucaLorenzini,AndreaBighinati,
AlessandroGiuliani,GiuseppeAlastra,MicaelaPannella,
MercedesFernandez,LucianaGiardino,andLauraCalzà
6 TheVersatileRolesofNerveGrowthFactorinNeuronal
Attraction,OdontoblastDifferentiation,andMineral
DepositioninHumanTeeth. . . . . . . . . . . . . . . . . . . . . . . . . . 65
ThimiosA.MitsiadisandPierfrancescoPagella
7 AnOverviewofAdultNeurogenesis. . . . . . . . . . . . . . . . . . . . 77
FilipaF.RibeiroandSaraXapelli
8 InterventionofBrain-DerivedNeurotrophicFactor
andOtherNeurotrophinsinAdultNeurogenesis. . . . . . . . . . 95
FilipaF.RibeiroandSaraXapelli
ix
x Contents
PartIII AlzheimerandCentralNervousSystem
9 RitaLevi-Montalcini,NGFMetabolisminHealthandinthe
Alzheimer’sPathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
A.ClaudioCuello
10 NGFandtheAmyloidPrecursorProteininAlzheimer’s
Disease:FromMolecularPlayerstoNeuronalCircuits. . . . . 145
VivianaTriaca,FrancescaRuberti,andNadiaCanu
11 AReviewofTechniquesforBiodeliveryofNerveGrowth
Factor(NGF)totheBraininRelationtoAlzheimer’s
Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
SumontoMitra,RuchiGera,BengtLinderoth,GöranLind,
LarsWahlberg,PerAlmqvist,HomiraBehbahani,
andMariaEriksdotter
12 NGFReleasedfromBloodCellsorCollagenHydrogels
asaTherapeuticTargetinAlzheimer’sDisease?. . . . . . . . . . 193
ChristianHumpel
PartIV ComplexBehaviors
13 WhenNerveGrowthFactorMetBehavior. . . . . . . . . . . . . . 205
DanielaSantucci,AriannaRacca,andEnricoAlleva
14 CrossTalkofBDNFandGDNFinSpinalSubstantia
Gelatinosa(LaminaII):FocusonCircuitry. . . . . . . . . . . . . . 215
AdalbertoMerighi
PartV ClinicalMedicine
15 BDNFGeneasaPrecisionSkillofObesityManagement. . . . 233
HelenaMarcos-Pasero,ElenaAguilar-Aguilar,
MariaP.Ikonomopoulou,andVivianaLoria-Kohen
16 TheScienceofLove:StateoftheArt. . . . . . . . . . . . . . . . . . . 249
DonatellaMarazziti,StefaniaPalermo,andFedericoMucci
17 NGFandRetinitisPigmentosa:StructuralandMolecular
Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255
MariaLuisaRocco,LauraCalzà,andLuigiAloe
18 NGFinInflammatoryandNeurodegenerativeDiseases
oftheEye:NewFindingsSupportingNeuroprotectionand
ProperTissueRemodelinginVitreoretinalDisorders. . . . . . 265
GrazianaEsposito,BijornOmarBalzamino,LucaBruno,
AndreaCacciamani,andAlessandraMicera