Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/141815
Title: | Unveiling the olfactory proteostatic dissangement in Parkinson's disease by proteome-wide profiling |
Author: | Lachén Montes, Mercedes González Morales, Andrea Iloro, Ibon Elortza, Felix Ferrer, Isidro (Ferrer Abizanda) Gveric, Djordje Fernández Irigoyen, Joaquín Santamaría, Enrique |
Keywords: | Olfacte Malaltia de Parkinson Proteòmica Biologia de sistemes Smell Parkinson's disease Proteomics Systems biology |
Issue Date: | 1-Jan-2019 |
Publisher: | Elsevier B.V. |
Abstract: | Olfactory 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. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1016/j.neurobiolaging.2018.09.018 |
It is part of: | Neurobiology of Aging, 2019, vol. 73, p. 123-134 |
URI: | http://hdl.handle.net/2445/141815 |
Related resource: | https://doi.org/10.1016/j.neurobiolaging.2018.09.018 |
ISSN: | 0197-4580 |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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