ArticleBiology of sex differences2023
Sex-divergent effects on the NAD+-dependent deacetylase sirtuin signaling across the olfactory-entorhinal-amygdaloid axis in Alzheimer's and Parkinson's diseases.
Article in Biology of sex differences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 20 citations in OpenAlex.
- Olfactory proteomics reveals the capacity of the HDAC1 inhibitor pyroxamide to halt the α-synuclein preformed fibrils-induced damage in nasal epithelial, microglial and dopaminergic neuronal cell lines.Brain pathology (Zurich, Switzerland) · 2026Article
- Mechanism of action of synaptic mitochondrial damage in delayed cognitive recovery.Neural regeneration research · 2026Article
- Early, sex-dependent and progressive proteomic imbalance in the amygdala during Alzheimer´s disease continuum.Biology of sex differences · 2026Article
- Research advances in key genes and regulatory mechanisms of posttranslational modifications in Parkinson's disease.PloS one · 2026Article
- Sex-related differences in phenotype and nigro-striatal degeneration of c-relBiology of sex differences · 2025Article
- Unraveling Potential Tauopathy Biomarkers in Cerebrospinal Fluid: Insights from Olfactory Tract Data.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Sirtuin insights: bridging the gap between cellular processes and therapeutic applications.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Article
- Review
- Proteoform Analysis of the Human Olfactory System: A Window into Neurodegenerative Diseases.Proteomes · 2024Review
- Downregulation of Sirtuin 1 Does Not Account for the Impaired Long-Term Potentiation in the Prefrontal Cortex of Female APPswe/PS1dE9 Mice Modelling Alzheimer's Disease.International journal of molecular sciences · 2023Article
- Towards Precision Prognostication and Personalized Therapeutics through Proteomics.International journal of molecular sciences · 2023Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundSmell impairment is one of the earliest features in Alzheimer's (AD) and Parkinson's diseases (PD). Due to sex differences exist in terms of smell and olfactory structures as well as in the prevalence and manifestation of both neurological syndromes, we have applied olfactory proteomics to favor the discovery of novel sex-biased physio-pathological mechanisms and potential therapeutic targets associated with olfactory dysfunction.
methodsSWATH-MS (sequential window acquisition of all theoretical fragment ion spectra mass spectrometry) and bioinformatic workflows were applied in 57 post-mortem olfactory tracts (OT) derived from controls with no known neurological history (n = 6F/11M), AD (n = 4F/13M) and PD (n = 7F/16M) subjects. Complementary molecular analyses by Western-blotting were performed in the olfactory bulb (OB), entorhinal cortex (EC) and amygdala areas.
results327 and 151 OT differentially expressed proteins (DEPs) were observed in AD women and AD men, respectively (35 DEPs in common). With respect to PD, 198 DEPs were identified in PD women, whereas 95 DEPs were detected in PD men (20 DEPs in common). This proteome dyshomeostasis induced a disruption in OT protein interaction networks and widespread sex-dependent pathway perturbations in a disease-specific manner, among them Sirtuin (SIRT) signaling. SIRT1, SIRT2, SIRT3 and SIRT5 protein levels unveiled a tangled expression profile across the olfactory-entorhinal-amygdaloid axis, evidencing disease-, sex- and brain structure-dependent changes in olfactory protein acetylation.
conclusionsAlteration in the OT proteostasis was more severe in AD than in PD. Moreover, protein expression changes were more abundant in women than men independent of the neurological syndrome. Mechanistically, the tangled SIRT profile observed across the olfactory pathway-associated brain regions in AD and PD indicates differential NAD (+)-dependent deacetylase mechanisms between women and men. All these data shed new light on differential olfactory mechanisms across AD and PD, pointing out that the evaluation of the feasibility of emerging sirtuin-based therapies against neurodegenerative diseases should be considered with caution, including further sex dimension analyses in vivo and in clinical studies.
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