Breaking down and building up alpha-synuclein: An insight on its N-terminaldomain
Alpha-synuclein (αSyn) is a small presynapticprotein (14kDa) that is involved in
synucleinopathies including Parkinson’sdisease (PD). In itsnativestate, theαSyn
monomerexistsinanunfoldedstate,anditsfoldingishighlydependentonvariations
of environmental conditions,mutations and interactionswithendogenous and/or
exogenousmolecules. Recently, there is increasingevidence for adirect interplay
betweenαSynandmicrotubules(MTs),whosedefectsarelinkedtoneurodegenera
tivediseases, suchasPD.Understanding thecorrelationbetweenαSynandMTs
couldbefundamental forthecorrectcomprehensionoftheundergoingmechanisms
ofPD.Hence,wechemicallysynthesizeda library of peptides, derivingfromboth
nativeandPDmutatedsequencesoftheN-terminaldomainofαSyn.Theirsecond
arystructurewascharacterizedbycirculardichroismandFouriertransforminfrared
(FTIR)experiments, inordertoevaluatetheeffectofPDmutations.Finally,thekinet
icsofpolymerizingtubulininvitrointhepresenceofthepeptideswasevaluated.
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