Table Of ContentKamal Dua · Raimar Löbenberg
Ângela Cristina Malheiros Luzo
Shakti Shukla · Saurabh Satija Editors
Targeting
Cellular
Signalling
Pathways in
Lung Diseases
Targeting Cellular Signalling Pathways
in Lung Diseases
(cid:129) (cid:129)
Kamal Dua Raimar Löbenberg
(cid:129)
Ângela Cristina Malheiros Luzo
(cid:129)
Shakti Shukla Saurabh Satija
Editors
Targeting Cellular
Signalling Pathways
in Lung Diseases
Editors
KamalDua RaimarLöbenberg
GraduateSchoolofHealth,Discipline DrugDevelopmentandInnovationCentre
ofPharmacy UniversityofAlberta
UniversityofTechnologySydney Edmonton,AB,Canada
Sydney,NSW,Australia
ÂngelaCristinaMalheirosLuzo ShaktiShukla
HaematologyandHemotherapyCenter GraduateSchoolofHealth,Discipline
StateUniversityofCampinas ofPharmacy
Campinas,SãoPaulo,Brazil UniversityofTechnologySydney
Sydney,NSW,Australia
SaurabhSatija
SchoolofPharmaceuticalSciences&
DivisionofResearch&Development
LovelyProfessionalUniversity
Phagwara,Punjab,India
ISBN978-981-33-6826-2 ISBN978-981-33-6827-9 (eBook)
https://doi.org/10.1007/978-981-33-6827-9
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Preface
Chronic lung diseases are among the leading causes of mortality and morbidity
globally and are significantly associated with the economic burden as well as
drasticallyreducedqualityoflifeandproductivity.Thecurrentlyavailabletherapies
aremostlyeffectiveinmanagingtheaggravatedsymptomsassociatedwiththelung
diseases, especially the non-communicable diseases such as asthma and chronic
obstructive pulmonary disease (COPD). This warrants consistent rigorous research
into discovering novel therapeutic targets that could be then harnessed pharmaco-
logicallytoimprovethequalityoflifeofpatients.Thiswouldrequireunderstanding
the underlying central/key molecular mechanisms that are generally referred as
“disease drivers.” Various molecules that drive the disease are key immune cells,
associatedcytokinesorchemokines,disease-associated genes, microRNAs, signal-
lingpathways,pathogen/damageassociatemoleculessensingreceptorsanddisease-
associatedoxidativestressmolecules/pathways.Anotherkeyaspectofmanagement
of lung diseases involves lack of effective drug delivery strategies that could
improve the bioavailability and subsequent efficacy of the existing/upcoming
therapies.
The primary objective of this book, Targeting Cellular Signalling Pathways in
Lung Diseases, is to comprehensively provide an overview of various cellular and
molecular mechanisms involved in chronic lung diseases and then to suggest the
currently available or upcoming therapeutic targets that could be efficacious in
managingthesediseases.Thebookadequatelyhighlightsamyriadofdrugdelivery
approaches that could be developed and tested before implementing in real-life
scenarios for improvingthedrugbioavailabilityandefficacy inlungs and/or target
cells/tissues/pathways. Collectively, the book could be immensely informative for
readerswhoareinterestedinrecentdevelopmentsinlungdiseasesintermsofnovel
mechanisms that could be targeted therapeutically, as well as the innovative drug
delivery systems that may become mainstream in coming years for effectively
treatingthelungregions/cells/pathwaysthatdemonstrateassociatedpathology.
Thebookrightlybeginswithanelaboratedintroductiontothelungdiseasesand
then expands to the comprehensive chapters covering the crucial pathological
mechanisms in non-communicable respiratory diseases, i.e., asthma, chronic
obstructive pulmonary disease, lung cancer, and idiopathic pulmonary fibrosis.
Thereafter, the book contains comprehensive chapters on microbial infections of
v
vi Preface
thelung,suchastuberculosis,Haemophilusinfluenzae,andviralinfections(includ-
ing the novel Coronavirus Disease 2019). This section is followed by chapters
comprising discussions around the master molecular regulators of lung diseases,
including,phosphoinositide3-kinase,thecholinergicsystem,Nrf2-Keap1signalling
pathway, Toll-like receptor (TLR). There is a dedicated subsection on the impor-
tanceofplant-basedornaturalcompoundsthatcouldbepotentialinthemanagement
oflungdiseases.Thefinalsectionofbookexclusivelysummarizestheprospectsand
challenges in developing and validating various drug delivery systems for respira-
torydiseases.Thechaptersinthebookhaveextensivevisualillustrationsthatmake
iteasierforreaderstounderstandthecomplexdiseasemechanisms.
We believe that this book will be a valuable resource for academicians,
researchers, and industry engaged in the field of respiratory biology. It is also a
valuable resource for translational researchers, graduates, and postgraduates (Mas-
ter’s,PhD,andPost-DoctoralResearchers)ofvariousdisciplinesincludingPharma-
ceuticalSciences,Biotechnology,Immunology,andMedicalandHealthSciences.
The editorial team has extensive research experience in the field of respiratory
diseases, respiratory infections, lung inflammation, and drug delivery systems for
respiratory system. The editors of this book would like to express their sincere
gratitude toall the authorsfor their time andfor their valuablecontributions inthe
productionofthisbook.
Sydney,NSW,Australia KamalDua
Edmonton,AB,Canada RaimarLöbenberg
Campinas,SãoPaulo,Brazil ÂngelaCristinaMalheirosLuzo
Sydney,NSW,Australia ShaktiShukla
Phagwara,Punjab,India SaurabhSatija
Acknowledgment
The publication of this book was finalized during the coronavirus (COVID-19)
pandemic. We would like to dedicate this book to all those who were affected by
thepandemicand,inparticular, toour health workforce around the world for their
dedicationandcareduringthisdifficulttime.
vii
Contents
1 IntroductiontoLungDiseases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ShivrajPopatJadhav,HimmatSingh,SalmanHussain,RituGilhotra,
AnuragMishra,ParteekPrasher,AnandKrishnan,andGauravGupta
2 TargetingMolecularandCellularMechanismsinAsthma. . . . . . . 27
ArchitaRay,SabitaSingh,JoytriDutta,andUlaganathanMabalirajan
3 VariousCellularandMolecularAxisInvolvedinthePathogenesis
ofAsthma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
GurjitKaurBhatti,AmitKhurana,DebapriyaGarabadu,
PrashantGupta,SnehalSainathJawalekar,JasvinderSinghBhatti,
andUmashankerNavik
4 TargetingMolecularandCellularMechanismsin
Steroid-ResistantAsthma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
JoytriDutta,SabitaSingh,ArchitaRay,andUlaganathanMabalirajan
5 TargetingMolecularandCellularMechanismsinChronic
ObstructivePulmonaryDisease. . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
ShvetankBhatt,JovitaKanoujia,A.N.Nagappa,
andK.SreedharaR.Pai
6 ProbingtheCellularandMolecularMechanismsUnderlyingin
thePathogenesisofChronicObstructivePulmonaryDisease. . . . . 147
C.SarathChandran,AlanRaj,andT.K.ShahinMuhammed
7 ChronicObstructivePulmonaryDisease:MolecularBasisof
PathogenesisandTargetedTherapeuticApproaches. . . . . . . . . . . . 163
SushwetaMahalanobish,SayantaDutta,andParamesC.Sil
8 Exploringthe‘DormancyActivationSwitch’intheTumour
MicroenvironmentforMetastaticLungCancer:ThePossible
RoleofMicroRNA. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
AmnaniAminuddin,SitiFathiahMasre,Sin-YeangTeow,
andPeiYuenNg
iixx
x Contents
9 TherapeuticStrategiesTargetingSignalingPathwaysinLung
Cancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217
GurjitKaurBhatti,ParasPahwa,AnshikaGupta,UmashankerNavik,
andJasvinderSinghBhatti
10 ModulationofSignalingPathwaysbyImmunotherapeutics
inLungCancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241
ParamitaMandal,AninditaGoswami,SarmisthaAdhikari,
andSubhamSarkar
11 UnderpinningtheCellularandMolecularMechanismswith
NanotheranosticsforLungCancer. . . . . . . . . . . . . . . . . . . . . . . . . 263
AsiyaMahtab,MonikaYadav,KarishmaNiveria,
andAnitaKamraVerma
12 TargetingMolecularandCellularMechanismsinIdiopathic
PulmonaryFibrosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287
BanudeviSivananthamandVijayageethaBose
13 ARefinedApproachtoTargettheMolecularandCellular
MechanismsinPulmonaryFibrosis. . . . . . . . . . . . . . . . . . . . . . . . . 311
SabitaSingh,JoytriDutta,ArchitaRay,AshishJaiswal,
andUlaganathanMabalirajan
14 TargetingMolecularandCellularMechanismsinTuberculosis. . . 337
LubhanSingh,KamalDua,SokindraKumar,DeepakKumar,
andSagarikaMajhi
15 CellularandMolecularMechanismsofRepurposedAntidiabetic
DrugasanAdjunctiveTreatmentforTuberculosis. . . . . . . . . . . . . 355
RupeshK.Gautam,RituMishra,KanikaSharma,andManjuSharma
16 TargetingHostandBacterialSignalingPathwaysinTuberculosis:
AnEffectiveStrategyfortheDevelopmentofNovel
Anti-tubercularTherapies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373
SamreenFatima,BhavyaBhardwaj,andVedPrakashDwivedi
17 TargetingMolecularandCellularMechanismsinPulmonary
Hypertension. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 395
StephenA.Adefegha,OlorunfemiR.Molehin,
andAderonkeE.Fakayode
18 TargetingMolecularandCellularMechanismsofPulmonary
ArterialHypertension. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 407
MdKhademAli,JayC.Horvat,andEddaF.Spiekerkoetter
Contents xi
19 PotentialCellularTargetsAssociatedwiththeSignalingofthe
PulmonaryHypertension. .. . . . .. . . . .. . . . .. . . . .. . . . .. . . . .. 435
MeemanshaSharma,ThakurUttamSingh,
MadhuCholanhalliLingaraju,andSubhashreeParida
20 TargetingMolecularandCellularMechanismofInfluenza
AVirus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 447
GayathriGopal,ShibiMuralidar,andSenthilVisagaAmbi
21 UnderstandingtheBiologyofNon-typeableHaemophilusinfluenzae
inChronicObstructivePulmonaryDiseaseThroughtheLensof
Genomics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 471
RajendraKCandRonanF.O’Toole
22 TargetingMolecularandCellularMechanisminRhinovirus
Infection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 485
ManjuandPranavKumarPrabhakar
23 TargetingMolecularandCellularMechanismsinRespiratory
SyncytialVirus(RSV)Infection. . . . . . . . . . . . . . . . . . . . . . . . . . . 501
PoojaMittal,RamitKapoor,AnjaliSaharan,andRupeshK.Gautam
24 TargetingMolecularandCellularMechanismsin
SARS-CoV-2NovelCoronavirusDisease2019(COVID-19). . . . . . 517
SagarikaMajhi,KamalDua,ParteekPrasher,
HarlokeshNarayanYadav,andLubhanSingh
25 UnderpinningtheRudimentary/UnderlyingMechanisms
InvolvedinthePathogenesisofSARS-CoV-2(COVID-19)
inHumanLungCells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 537
ArnabGhosh,ChandrikaBhattacharyya,NidhanK.Biswas,
andAmlanDas
26 TargetingMolecularandCellularMechanismsin
SARS-CoV-2NovelCorona(COVID-19)VirusInfection. . . . . . . . 559
NabanitaRoyChattopadhyay,NilanjanaDas,
andTathagataChoudhuri
27 SpecialFeaturesofHumanLungACE2Sensitivityto
SARS-CoV-2SpikeGlycoprotein. . . . . . . . . . . . . . . . . . . . . . . . . . 583
DipannitaSantra,AmritaBanerjee,andSmarajitMaiti
28 ImplicationsofPhosphoinositide3-Kinase(PI3K)Signallingin
CellularandMolecularMechanismsofRespiratoryDiseases. . . . . 601
BiswarupBasu,SandipGhosh,SouvikDas,andAmlanDas
29 TheRoleoftheCholinergicSysteminLungDiseases. . . . . . . . . . . 625
VedranMilankovicandTamaraLazarevic-Pasti
30 TheKeap1-Nrf2SignalingPathwayinLungCancer. . . . . . . . . . . . 661
AzhwarRaghunath,RajuNagarajan,andKiruthikaSundarraj
