Natural Compounds as Therapeutic Agents for Amyloidogenic Diseases

167 Pages·2015·4.53 MB·English

by  Neville Vassallo (eds.)

Advances in Experimental Medicine and Biology 863
Neville Vassallo Editor
Natural Compounds
as Therapeutic
Agents for
Amyloidogenic
Diseases
Advances in Experimental Medicine
and Biology
Volume 863
EditorialBoard
IrunR.Cohen,TheWeizmannInstituteofScience,Rehovot,Israel
N.S.AbelLajtha,KlineInstituteforPsychiatricResearch,Orangeburg,NY,
USA
JohnD.Lambris,UniversityofPennsylvania,Philadelphia,PA,USA
RodolfoPaoletti,UniversityofMilan,Milan,Italy
Moreinformationaboutthisseriesathttp://www.springer.com/series/5584
Neville Vassallo
Editor
Natural Compounds as
Therapeutic Agents for
Amyloidogenic Diseases
123
Editor
NevilleVassallo
DepartmentofPhysiology
andBiochemistry
UniversityofMalta
Msida,Malta
ISSN0065-2598 ISSN2214-8019 (electronic)
AdvancesinExperimentalMedicineandBiology
ISBN978-3-319-18364-0 ISBN978-3-319-18365-7 (eBook)
DOI10.1007/978-3-319-18365-7
LibraryofCongressControlNumber:2015942700
SpringerChamHeidelbergNewYorkDordrechtLondon
©SpringerInternationalPublishingSwitzerland2015
Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewhole
orpartofthematerialisconcerned,specificallytherightsoftranslation,reprinting,reuseof
illustrations,recitation,broadcasting,reproductiononmicrofilmsorinanyotherphysicalway,
andtransmissionorinformationstorageandretrieval,electronicadaptation,computersoftware,
orbysimilarordissimilarmethodologynowknownorhereafterdeveloped.
Theuseofgeneraldescriptivenames,registerednames,trademarks,servicemarks,etc.inthis
publication does not imply, even in the absence of a specific statement, that such names are
exemptfromtherelevantprotectivelawsandregulationsandthereforefreeforgeneraluse.
Thepublisher,theauthorsandtheeditorsaresafetoassumethattheadviceandinformationin
thisbookarebelievedtobetrueandaccurateatthedateofpublication.Neitherthepublisher
northeauthorsortheeditorsgiveawarranty,expressorimplied,withrespecttothematerial
containedhereinorforanyerrorsoromissionsthatmayhavebeenmade.
Printedonacid-freepaper
SpringerInternationalPublishingAGSwitzerlandispartofSpringerScience+BusinessMedia
(www.springer.com)
Preface
A large group of human diseases are characterised by the deposition of
insolubleproteinaceouslesions,termedamyloid.Theunderlyingpathogenic
process in these disorders involves the misfolding and self-assembly of
nativemonomericproteinsintotoxic,multimericaggregates.Indeed,“protein
misfolding” is one of the most researched topics in cell biology and sub-
cellular biochemistry in recent years. To date, more than 20 amyloidogenic
proteinshavebeenidentified,includingamyloid-betaandtauinAlzheimer’s
disease, alpha-synuclein in Parkinson’s disease, huntigtin in Huntington’s
disease,superoxidedismutaseinamyotrophiclateralsclerosis,prionprotein
inCreutzfeldt-Jakobdiseaseandisletamyloidpolypeptideintype2diabetes
mellitus.Collectively,thesedisordersinflictanenormouseconomicalburden
on societies, whilst being devastating at a personal level. It is therefore of
paramount importance to understand their origin and learn how to treat, or
prevent,them.Atpresent,therearenoapprovedtherapiesthattargetamyloid
formationdirectly,butawealthofexperimentalandepidemiologicalevidence
nowindicatesthatvariousnaturallyderivedcompoundshavebeneficialanti-
amyloideffects.
This book volume was written with the aim of disseminating the state-
of-the-art and most recent knowledge of the field, highlighting the most
promising nutra-therapeutics derived from natural compounds or extracts.
The focus is mainly on Alzheimer’s disease and related dementias; how-
ever, Parkinson’s disease and other forms of cerebral amyloidosis are also
discussed. Evidence is presented based upon published studies that have
undergonerigorousscientificpeerreview.Researchesincludeacombination
ofinvitro(biophysics,biochemistry,molecularandcellularbiology),invivo
(fruit fly, transgenic mice and rats) and epidemiological (human) studies,
so as to provide the reader with a holistic scientific approach. Among the
therapeuticagentsthatarediscussedindetail,wefindMediterraneandietand
olive oil polyphenols, teas and catechins, natural phenolic compounds and
bioflavonoids.Giventherecentsurgeofpublicinterestinherbalmedicines,a
chapter is devoted to evidence-based traditional Chinese medicine in brain
ageing. Individual chapters are written by established scientists in their
relevant fields; sufficient background is given in each chapter by way of
introductiontothenon-expertreader.Hence,thisbookshouldbeofinterest
to a wide audience, including academia, various health professionals, the
nutraceuticalindustryandundergraduatestudentsreadingforpharmaceutical,
medical,biologyandchemistrydegrees.
v
vi Preface
Iconcludebystatingthat,onapersonallevel,themostnoblegoalofthis
bookisthatwithourcollectivecontributionstoscientificprogress,weaimto
provide hope for the future and hope for the many people suffering from as
yetincurableamyloiddiseases.Thisbookis,afterall,dedicatedtothem.
Msida,Malta NevilleVassallo
Contents
1 OliveOilPhenolsasPromisingMulti-targetingAgentsAgainst
Alzheimer’sDisease...................................... 1
StefaniaRigacci
2 Alzheimer’sDisease,Drosophilamelanogaster
andPolyphenols.......................................... 21
MarleneJimenez-Del-RioandCarlosVelez-Pardo
3 BiflavonoidsasPotentialSmallMoleculeTherapeuticsfor
Alzheimer’sDisease...................................... 55
ArjunThapaandEvaY.Chi
4 NaturalPhenolicCompoundsasTherapeuticandPreventive
AgentsforCerebralAmyloidosis........................... 79
MasahitoYamada, KenjiroOno, TsuyoshiHamaguchi,
andMoekoNoguchi-Shinohara
5 Brain Food for Alzheimer-Free Ageing: Focus on Herbal
Medicines............................................... 95
HelmutM.Hügel
6 TeaPolyphenolsinParkinson’sDisease..................... 117
MarioCaruanaandNevilleVassallo
7 The Effect of ((cid:2))-Epigallo-catechin-(3)-gallate
onAmyloidogenicProteinsSuggestsaCommonMechanism. . 139
KathrinAndrichandJanBieschke
Index....................................................... 163
vii
1
Olive Oil Phenols as Promising
Multi-targeting Agents Against
Alzheimer’s Disease
StefaniaRigacci
Abstract
Amyloid diseases are characterized by the deposition of typically
aggregated proteins/peptides in tissues, associated with degeneration
and progressive functional impairment. Alzheimer’s disease is one of
the most studied neurodegenerative amyloid diseases and, in Western
countries, a significant cause of dementia in the elderly. The so-called
“Mediterraneandiet”hasbeenconsideredforlongasthehealthierdietary
regimen, characterised by a great abundance in vegetables and fruits,
extra virgin olive oil as the main source of fat, a moderate consumption
of red wine and a reduced intake of proteins from red meat. Recent
epidemiological studies support the efficacy of the Mediterranean diet
not only against cardiovascular and cancer diseases (as previously
demonstrated) but also against the cognitive decline associated with
ageing, and several data are highlighting the role played by natural
phenols, of which red wine and extra virgin olive oil are rich, in such
context. In the meantime, studies conducted both in vivo and in vitro
have started to reveal the great potential of the phenolic component of
extra virgin olive oil (mainly oleuropein aglycone and oleocanthal) in
counteractingamyloidaggregationandtoxicity,withaparticularemphasis
on the pathways involved in the onset and progression of Alzheimer’s
disease:amyloidprecursorproteinprocessing,amyloid-beta(A“)peptide
and tau aggregation, autophagy impairment, neuroinflammation. The
aim of this review is to summarize the results of such research efforts,
S.Rigacci((cid:2))
DepartmentofExperimentalandClinicalBiomedical
Sciences“MarioSerio”,UniversityofFlorence,Viale
Morgagni50,50134Florence,Italy
e-mail:[email protected]
©SpringerInternationalPublishingSwitzerland2015 1
N.Vassallo(ed.),NaturalCompoundsasTherapeuticAgentsforAmyloidogenicDiseases,
AdvancesinExperimentalMedicineandBiology863,DOI10.1007/978-3-319-18365-7_1
2 S.Rigacci
showinghowtheactionofthesephenolsgoesfarbeyondtheirrenowned
antioxidantactivityandrevealingtheirpotentialasmulti-targetingagents
againstAlzheimer’sdisease.
Keywords
Alzheimer’s disease • Mediterranean diet • Polyphenols • Extra virgin
oliveoil•Oleuropeinaglycone
fish or cheese can be more-or-less abundant),
1.1 Introduction one ingredient should never be absent from
the Mediterranean table: EVOO, probably the
Age-associatedcognitivedecline,intherelatively most typical component of MD. EVOO consists
benignformofmildcognitiveimpairment(MCI) of 98 % glycerides, mainly monounsaturated
and in the more severe one of Alzheimer’s dis- fatty acids (MUFA). In any case, it is the
ease(AD),hasbecomeaconsiderablesocialand remaining 2 %, including various so-called
clinical problem during the last decades, partic- “minor compounds”, that deserves much of
ularly in Western countries. With the important our attention in this context. These consist of
exception of familial AD, which is associated ’-tocopherol and of several specific phenolic
with one of several genetic mutations favouring compounds including phenolic acids (caffeic,
theearlyonsetofthedisease,suchaconditionde- vanillic, syringic, p-coumaric, o-coumaric,
velopsoveraconsiderableperiodoftime,maybe protocatechuic, sinapic, p-hydroxybenzoic
even decades. Moreover, in spite of the great and gallic), phenolic alcohols (tyrosol and
efforts spent by researchers toidentify early and hydroxytyrosol),lignans(acetoxypinoresinoland
accessible markers of this disease, AD is still pinoresinol), flavones (apigenin and luteolin)
diagnosedverylate,whentheneurologicalsymp- and, last but not least, secoiridoids (oleuropein
tomsappearandtheneuropathologyisalreadyin aglycone,oleochantalandtheirderivatives).The
an advanced stage. For these reasons (life-long latterarethemostabundantandtypicalphenolic
development–latediagnosis–neuronalloss)two components of EVOO; hence investigations
importantbranchesoftheresearchinthisfieldare aimed at identifying the active principles
earlydiagnosisandprevention. responsible for the specific healthy benefits
With regards to prevention, a lot of attention of EVOO have been mainly focused on them
has been placed on the role played by (Servilietal.2009).
different lifestyles in favouring this disease. The concentration of these substances in oil
Epidemiological evidence points to a lower is highly variable, depending on a number of
incidence of MCI and AD in populations different factors: olive cultivar, ripening stage
adhering to the Mediterranean diet (MD), a at harvesting, geographic origin of olives, olive
dietary regimen that has already been strongly treesirrigation,operativeconditionsapplieddur-
associatedwithareducedriskforcardiovascular ing crushing, malaxation and oil separation, oil
diseases and cancer (Martinez-Gonzalez et al. storage modalities. The last two factors are par-
2011; Sofi et al. 2010; Benetou et al. 2008; ticularly relevant. In fact, the highest phenolic
Lopez-Mirandaetal.2010).MDischaracterized content is present in oil immediately after its
by extra virgin olive oil (EVOO), high intake coldmechanicalextractionfromolives(amanda-
of plant-based foods, relevant consumption toryproceduretoobtainanEVOO)andprogres-
of seafood, low-to moderate intake of dairy sively declines with oil ageing, particularly if it
products, low intake of meat and a regular is exposed to air and light that promote phenols
but moderate intake of red wine. In spite of oxidation and degradation. With some notable
regional and cultural variations (for example, exceptions, total phenols in olive oil generally