Lachén Montes, MercedesGonzález Morales, AndreaIloro, IbonElortza, FelixFerrer, Isidro (Ferrer Abizanda)Gveric, DjordjeFernández Irigoyen, JoaquínSantamaría, Enrique2019-10-072020-01-012019-01-010197-4580https://hdl.handle.net/2445/141815Olfactory dysfunction is one of the earliest features in Lewy-type alphasynucleinopathies (LTS) such as Parkinson´s disease (PD). However, the underlying molecular mechanisms associated to smell impairment are poorly understood. Applying mass spectrometry-based quantitative proteomics in postmortem olfactory bulbs (OB) across limbic, early-neocortical, and neocortical LTS stages of parkinsonian subjects, a proteostasis impairment was observed, identifying 268 differentially expressed proteins between controls and PD phenotypes. In addition, network-driven proteomics revealed a modulation in ERK1/2, MKK3/6, and PDK1/PKC signalling axis. Moreover, a crossdisease study of selected olfactory molecules in sporadic Alzheimer's disease (AD) cases, revealed different protein derangements in the modulation of Secretagogin (SCGN), Calcyclin binding protein (CACYBP), and Glucosamine 6 phosphate isomerase 2 (GNPDA2) between PD and AD. An inverse correlation between GNPDA2 and α-synuclein protein levels was also reflected in PD cerebrospinal fluid (CSF). Interestingly, PD patients exhibited significantly lower serum GNPDA2 levels than controls (n=82/group). Our study provides important avenues for understanding the OB proteostasis imbalance in PD, deciphering mechanistic clues to the equivalent smell deficits observed in AD and PD pathologies.12 p.application/pdfengcc-by-nc-nd (c) Elsevier B.V., 2019http://creativecommons.org/licenses/by-nc-nd/3.0/esOlfacteMalaltia de ParkinsonProteòmicaBiologia de sistemesSmellParkinson's diseaseProteomicsSystems biologyinfo:eu-repo/semantics/article6894472019-10-07info:eu-repo/semantics/openAccess30342273