Lachén Montes, MercedesMendizuri, NaroaAusín, KarinaAndrés Benito, PolFerrer, IsidroFernández Irigoyen, JoaquínSantamaría Martínez, Enrique2021-06-162021-06-1620201661-659610.3390/ijms21218311https://academica-e.unavarra.es/handle/2454/39938Incluye material complementarioAmyotrophic lateral sclerosis (ALS) is a fatal disease characterized by progressive muscle paralysis due to the degeneration of upper and lower motor neurons. Recent studies point out an involvement of the non-motor axis during disease progression. Despite smell impairment being considered a potential non-motor finding in ALS, the pathobiochemistry at the olfactory level remains unknown. Here, we applied an olfactory quantitative proteotyping approach to analyze the magnitude of the olfactory bulb (OB) proteostatic imbalance in ALS subjects (n = 12) with respect to controls (n = 8). Around 3% of the quantified OB proteome was differentially expressed, pinpointing aberrant protein expression involved in vesicle-mediated transport, macroautophagy, axon development and gliogenesis in ALS subjects. The overproduction of olfactory marker protein (OMP) points out an imbalance in the olfactory signal transduction in ALS. Accompanying the specific overexpression of glial fibrillary acidic protein (GFAP) and Bcl-xL in the olfactory tract (OT), a tangled disruption of signaling routes was evidenced across the OB–OT axis in ALS. In particular, the OB survival signaling dynamics clearly differ between ALS and frontotemporal lobar degeneration (FTLD), two faces of TDP-43 proteinopathy. To the best of our knowledge, this is the first report on high-throughput molecular characterization of the olfactory proteostasis in ALS.18 p.application/pdfapplication/zipeng© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.Amyotrophic lateral sclerosisOlfactory bulbOlfactory tractProteomicsSignalingTDP-43 proteinopathyinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessAcceso abierto / Sarbide irekia