Unveiling the olfactory proteostatic disarrangement in Parkinson's disease by proteome-wide profiling

Lachén-Montes, Mercedes; González-Morales, Andrea; Iloro, Ibón; Elortza, Félix; Ferrer, Isidre; Gverić, Djordje; Fernández‐Irigoyen, Joaquín; Santamaría, Enrique

doi:10.1016/j.neurobiolaging.2018.09.018

Cited by 43 publications

(49 citation statements)

References 70 publications

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“…Thus, the inhibition of the proapoptotic factor pBAD, together with the tendency to increase in BclxL protein suggests readjustments in the survival potential of the OB from DLB subjects. Previous reports have demonstrated a differential deregulation of multiple survival kinases in AD and PD at the level of the OB [ 39 , 40 , 42 ]. Subsequent experiments were performed to monitor upstream and downstream effectors of the following specific routes: (i) MAPK pathway: ERK1/2 (extracellular signal-regulated kinase 1/2) and MEK1/2 (mitogen-activated protein kinase kinase 1/2), (ii) SEK1 (mitogen-activated protein kinase kinase 4)-SAPK/JNK (stress-activated protein kinase/Jun-amino terminal kinase) axis, and (iii) the MKK3/6 (dual specificity mitogen-activated protein kinase kinase 3/6)-p38 MAPK axis.…”

Section: Resultsmentioning

confidence: 99%

“…However, the expression profiling detected in DLB ( Figure 3 C) differs from the observed during AD or PD progression. No alterations in AKT signaling have been previously observed during both AD and PD stage-dependent OB analysis [ 39 , 42 ]. On the other hand, previous work has demonstrated the activation of olfactory ERK survival factor during AD [ 42 ].…”

Section: Resultsmentioning

confidence: 99%

“…Thus, tissue-based quantitative clinical proteomics has already been aimed to provide more insights into DLB pathology [ 33 , 34 , 35 , 36 ]. However, although olfactory proteomics has been successfully applied in neurodegenerative phenotypes in mice and humans [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ], the olfactory proteostatic imbalance that occurs in DLB remains unknown. To our knowledge, this is the first study aiming to decipher the specific molecular mechanisms that underlie the process of neurodegeneration at the level of primary olfactory areas in DLB.…”

Section: Introductionmentioning

confidence: 99%

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Proteomic Characterization of the Olfactory Molecular Imbalance in Dementia with Lewy Bodies

Lachén-Montes

Mendizuri

Schvartz

et al. 2020

IJMS

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Olfactory dysfunction is one of the prodromal symptoms in dementia with Lewy bodies (DLB). However, the molecular pathogenesis associated with decreased smell function remains largely undeciphered. We generated quantitative proteome maps to detect molecular alterations in olfactory bulbs (OB) derived from DLB subjects compared to neurologically intact controls. A total of 3214 olfactory proteins were quantified, and 99 proteins showed significant alterations in DLB cases. Protein interaction networks disrupted in DLB indicated an imbalance in translation and the synaptic vesicle cycle. These alterations were accompanied by alterations in AKT/MAPK/SEK1/p38 MAPK signaling pathways that showed a distinct expression profile across the OB–olfactory tract (OT) axis. Taken together, our data partially reflect the missing links in the biochemical understanding of olfactory dysfunction in DLB.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Proteomic Characterization of the Olfactory Molecular Imbalance in Dementia with Lewy Bodies

Lachén-Montes

Mendizuri

Schvartz

et al. 2020

IJMS

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“…GNPDA2 was overexpressed in PD and AD cases and showed lower serum levels in PD patients. Interestingly, in PD patients, GNPDA2 showed an inverse correlation with α-synulein protein levels in the cerebrospinal fluid ( Lachén-Montes et al, 2019 ), suggesting its implication in developing PD.…”

Section: Genes Associated With Obesity and Neurodegenerative And Neurmentioning

confidence: 99%

“…Meta-analysis from PD GWAS report over 30 variants close to genes like CTSB , TMEM175 , LRRK2 , among others ( Nalls et al, 2014 ; Chang et al, 2018 ). Some of the common genes that have been associated with obesity and PD are: GNPDA2 ( Lachén-Montes et al, 2019 ) CD38 , TNFα , and PAI-1 ( Pan et al, 2018 ) that will be discussed below.…”

Section: Genes Associated With Obesity and Neurodegenerative And Neurmentioning

confidence: 99%

Environment and Gene Association With Obesity and Their Impact on Neurodegenerative and Neurodevelopmental Diseases

2020

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Obesity is a multifactorial disease in which environmental conditions and several genes play an important role in the development of this disease. Obesity is associated with neurodegenerative diseases (Alzheimer, Parkinson, and Huntington diseases) and with neurodevelopmental diseases (autism disorder, schizophrenia, and fragile X syndrome). Some of the environmental conditions that lead to obesity are physical activity, alcohol consumption, socioeconomic status, parent feeding behavior, and diet. Interestingly, some of these environmental conditions are shared with neurodegenerative and neurodevelopmental diseases. Obesity impairs neurodevelopment abilities as memory and fine-motor skills. Moreover, maternal obesity affects the cognitive function and mental health of the offspring. The common biological mechanisms involved in obesity and neurodegenerative/neurodevelopmental diseases are insulin resistance, pro-inflammatory cytokines, and oxidative damage, among others, leading to impaired brain development or cell death. Obesogenic environmental conditions are not the only factors that influence neurodegenerative and neurodevelopmental diseases. In fact, several genes implicated in the leptin–melanocortin pathway ( LEP , LEPR , POMC , BDNF , MC4R , PCSK1 , SIM1 , BDNF , TrkB , etc.) are associated with obesity and neurodegenerative and neurodevelopmental diseases. Moreover, in the last decades, the discovery of new genes associated with obesity ( FTO, NRXN3, NPC1, NEGR1, MTCH2, GNPDA2 , among others) and with neurodegenerative or neurodevelopmental diseases ( APOE, CD38, SIRT1, TNF α, PAI-1, TREM2, SYT4, FMR1, TET3 , among others) had opened new pathways to comprehend the common mechanisms involved in these diseases. In conclusion, the obesogenic environmental conditions, the genes, and the interaction gene–environment would lead to a better understanding of the etiology of these diseases.

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Combination of Antibody Arrays to Functionally Characterize Dark Proteins in Human Olfactory Neuroepithelial Cells

Lachén-Montes

Ausín

Cartas-Cejudo

et al. 2021

Methods in Molecular Biology

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Unveiling the olfactory proteostatic disarrangement in Parkinson's disease by proteome-wide profiling

Cited by 43 publications

References 70 publications

Proteomic Characterization of the Olfactory Molecular Imbalance in Dementia with Lewy Bodies

Proteomic Characterization of the Olfactory Molecular Imbalance in Dementia with Lewy Bodies

Environment and Gene Association With Obesity and Their Impact on Neurodegenerative and Neurodevelopmental Diseases

Combination of Antibody Arrays to Functionally Characterize Dark Proteins in Human Olfactory Neuroepithelial Cells

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