Lipid chaperones and associated diseases: a group of chaperonopathies defining a new nosological entity with implications for medical research and practice

D’Anneo, Antonella; Bavisotto, Celeste Caruso; Gammazza, Antonella Marino; Paladino, Letizia; Carlisi, Daniela; Cappello, Francesco; Macario, Everly Conway de; Macario, Alberto J. L.; Lauricella, Marianna

doi:10.1007/s12192-020-01153-6

Cited by 23 publications

(23 citation statements)

References 130 publications

(205 reference statements)

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“…H-FABP is a sensitive biomarker for cardiovascular risk factors [ 32 ]. FABP-Adipocytes (FABPA) is overexpressed with obesity as well as correlated with blood pressure and dyslipidemia [ 33 ]. The post hoc analysis adjusted for confounders including body composition and physical inactivity reduced the significance of leptin and FABPA, supporting a role for obesity in frailty progression.…”

Section: Discussionmentioning

confidence: 99%

Trajectories of frailty in aging: Prospective cohort study

et al. 2021

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Background Emerging evidence suggests that there is significant variability in the progression of frailty in aging. We aimed to identify latent subpopulations of frailty trajectories, and examine their clinical and biological correlates. Methods We characterized frailty using a 41-item cumulative deficit score at baseline and annual visits up to 12 years in 681 older adults (55% women, mean age 74·6 years). Clinical risk profile and walking while talking performance as a clinical marker of trajectories were examined. Mortality risk associated with trajectories was evaluated using Cox regression adjusted for established survival predictors, and reported as hazard ratios (HR). Proteome-wide analysis was done. Findings Latent class modeling identified 4 distinct frailty trajectories: relatively stable (34·4%) as well as mild (36·1%), moderate (24·1%) and severely frail (5·4%). Four distinct classes of frailty trajectories were also shown in an independent sample of 515 older adults (60% women, 68% White, 26% Black). The stable group took a median of 31 months to accumulate one additional deficit compared to 20 months in the severely frail group. The worst trajectories were associated with modifiable risk factors such as low education, living alone, obesity, and physical inactivity as well as slower walking while talking speed. In the pooled sample, mild (HR 2·33, 95% CI 1·30–4·18), moderate (HR 2·49, 95% CI 1·33–4·66), and severely frail trajectories (HR 5·28, 95% CI 2·68–10·41) had higher mortality compared to the stable group. Proteomic analysis showed 11 proteins in lipid metabolism and growth factor pathways associated with frailty trajectories. Conclusion Frailty shows both stable and accelerated patterns in aging, which can be distinguished clinically and biologically.

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Section: Discussionmentioning

confidence: 99%

Trajectories of frailty in aging: Prospective cohort study

et al. 2021

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“…The highest concentration of that protein in the AD patients and correlation with Tau and pTau181 in MCI subjects and Tau in AD patients may suggest the association with the neurodegeneration process. The fact that FABP3 in the brain may also regulate the neuronal membrane’s lipid composition could affect synaptic plasticity and cholinergic activity, glutamatergic, and especially GABAergic inhibitory interneurons [ 22 , 27 , 42 , 43 ]. We suggest that FABP3 play a pivotal role in the development of cognitive decline.…”

Section: Discussionmentioning

confidence: 99%

“…Mounting evidence suggests that Fatty acid-binding protein 3 (FABP3), heart-type (hFABP), may influence neurodegeneration and probable AD development [ 22 , 23 , 24 ]. FABP3 is expressed in the heart and nervous system (e.g., cerebral neocortex and hippocampal CA1 and CA2 region), especially in dopaminergic, acetylocholinergic and glutamatergic neurones [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Fatty Acid Binding Protein 3 (FABP3) and Apolipoprotein E4 (ApoE4) as Lipid Metabolism-Related Biomarkers of Alzheimer’s Disease

Dulewicz

Kulczyńska-Przybik

Słowik

et al. 2021

JCM

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Background: Lipid metabolism-related biomarkers gain increasing researchers interest in the field of neurodegenerative disorders. Mounting evidence have indicated the role of fatty acid-binding proteins and pathology lipid metabolism in Alzheimer’s Disease (AD). The imbalance of fatty acids (FA) and lipids may negatively affect brain functions related to neurodegenerative disorders. The ApoE4 and FABP3 proteins may reflect processes leading to neurodegeneration. This study aimed to evaluate the relationship between the CSF levels of FABP3 and ApoE4 proteins and cognitive decline as well as the diagnostic performance of these candidate biomarkers in AD and mild cognitive impairment (MCI). Methods: A total of 70 subjects, including patients with AD, MCI, and non-demented controls, were enrolled in the study. CSF concentrations of FABP3 and ApoE4 were measured using immunoassay technology. Results: Significantly higher CSF concentrations of FABP3 and ApoE4 were observed in AD patients compared to MCI subjects and individuals without cognitive impairment. Both proteins were inversely associated with Aβ42/40 ratio: ApoE4 (rho = −0.472, p < 0.001), and FABP3 (rho = −0.488, p < 0.001) in the whole study group, respectively. Additionally, FABP3 was negatively correlated with Mini-Mental State Examination score in the whole study cohort (rho = −0.585 p < 0.001). Conclusion: Presented results indicate the pivotal role of FABP3 and ApoE4 in AD pathology as lipid-related biomarkers, but studies on larger cohorts are needed.

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“…FABPs perform pleiotropic functions to maintain healthy tissue homeostasis, and participate in the pathogenesis of diseases [ 16 ]. To date, at least 10 genes encoding FABPs ( FABP1-9 and FABP12 ) have been identified in the human genome [ 17 , 18 ]. FABP5 localizes to the cytosol, mitochondria, and nucleus, suggesting a role for fatty acid metabolism and nuclear transcriptional regulation [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Epidermal Fatty Acid-Binding Protein 5 (FABP5) Involvement in Alpha-Synuclein-Induced Mitochondrial Injury under Oxidative Stress

et al. 2021

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The accumulation of α-synuclein (αSyn) has been implicated as a causal factor in the pathogenesis of Parkinson’s disease (PD). There is growing evidence that supports mitochondrial dysfunction as a potential primary cause of dopaminergic neuronal death in PD. Here, we focused on reciprocal interactions between αSyn aggregation and mitochondrial injury induced by oxidative stress. We further investigated whether epidermal fatty acid-binding protein 5 (FABP5) is related to αSyn oligomerization/aggregation and subsequent disturbances in mitochondrial function in neuronal cells. In the presence of rotenone, a mitochondrial respiratory chain complex I inhibitor, co-overexpression of FABP5 with αSyn significantly decreased the viability of Neuro-2A cells compared to that of αSyn alone. Under these conditions, FABP5 co-localized with αSyn in the mitochondria, thereby reducing mitochondrial membrane potential. Furthermore, we confirmed that pharmacological inhibition of FABP5 by its ligand prevented αSyn accumulation in mitochondria, which led to cell death rescue. These results suggested that FABP5 is crucial for mitochondrial dysfunction related to αSyn oligomerization/aggregation in the mitochondria induced by oxidative stress in neurons.

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Lipid chaperones and associated diseases: a group of chaperonopathies defining a new nosological entity with implications for medical research and practice

Cited by 23 publications

References 130 publications

Trajectories of frailty in aging: Prospective cohort study

Trajectories of frailty in aging: Prospective cohort study

Fatty Acid Binding Protein 3 (FABP3) and Apolipoprotein E4 (ApoE4) as Lipid Metabolism-Related Biomarkers of Alzheimer’s Disease

Epidermal Fatty Acid-Binding Protein 5 (FABP5) Involvement in Alpha-Synuclein-Induced Mitochondrial Injury under Oxidative Stress

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