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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
Biologia de sistemes
Parkinson's disease
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:
It is part of: Neurobiology of Aging, 2019, vol. 73, p. 123-134
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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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