Carregant...
Fitxers
Tipus de document
ArticleVersió
Versió acceptadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/141815
Unveiling the olfactory proteostatic dissangement in Parkinson's disease by proteome-wide profiling
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
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.
Matèries (anglès)
Citació
Citació
LACHÉN MONTES, Mercedes, GONZÁLEZ MORALES, Andrea, ILORO, Ibon, ELORTZA, Felix, FERRER, Isidro (ferrer abizanda), GVERIC, Djordje, FERNÁNDEZ IRIGOYEN, Joaquín, SANTAMARÍA, Enrique. Unveiling the olfactory proteostatic dissangement in Parkinson's disease by proteome-wide profiling. _Neurobiology of Aging_. 2019. Vol. 73, núm. 123-134. [consulta: 23 de gener de 2026]. ISSN: 0197-4580. [Disponible a: https://hdl.handle.net/2445/141815]