Characterization of the novel protein P9TLDR (temporal lobe down‐regulated) with a brain‐site‐specific gene expression modality in Alzheimer's disease brain

摘要

Alzheimer'sdisease(AD)isanaging‐relatedneurodegenerativedisordercharacterizedbyirreversiblelossofhighercognitivefunctions.Thediseaseischaracterizedbythepresenceofamyloidplaquesandneurofibrillarytangles(NFT).Inthecurrentstudyweisolatedfromanintra‐cerebralbrain‐site‐specific(ADtemporallobevs.ADoccipitallobe)polymerasechainreaction(PCR)‐selectcDNAsuppressionsubtractivehybridization(PCR‐cDNA‐SSH)expressionanalysisthenovelgeneP9TLDR,potentiallyamicrotubule‐associatedproteininvolvedinneuronalmigration,withanalteredexpressionpattern:down‐regulatedinthetemporallobecortexofearlystageADbrains.InaninvitroAD‐relatedcellmodel,amyloid‐βpeptide(Aβ)‐treatedneurons,reducedP9TLDRexpressioncorrelatedwithincreasedtauproteinphosphorylation.Inconclusion,interferencewiththeP9TLDRsignallingpathwaysmightbeatherapeuticstrategyforthetreatmentofAD...