Mechanistic perspectives on differential mitochondrial-based neuroprotective effects of several carnitine forms in Alzheimer’s disease in vitro model

Mota, Sandra I.; Pita, Inês; Águas, Rodolfo; Tagorti, Slah; Virmani, Ashraf; Pereira, Frederico C.; Rego, A. Cristina

doi:10.1007/s00204-021-03104-1

Cited by 16 publications

(14 citation statements)

References 62 publications

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“…Serum levels of ALCAR and CSF levels of L-carnitine are decreased in AD [129,347]. In primary neurons, ALCAR ameliorates Ab-oligomerevoked changes in mitochondrial respiration, fragmentation, and movement [348]. Animal studies show that ALCAR improves age-associated mitochondrial dysfunction and cognitive deficit [349,350].…”

Section: Reducing Lipid Accumulationsmentioning

confidence: 99%

Lipid metabolism and Alzheimer's disease: clinical evidence, mechanistic link and therapeutic promise

Yin

2022

The FEBS Journal

112

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Alzheimer’s disease (AD) is an age‐associated neurodegenerative disorder with multifactorial etiology, intersecting genetic and environmental risk factors, and a lack of disease‐modifying therapeutics. While the abnormal accumulation of lipids was described in the very first report of AD neuropathology, it was not until recent decades that lipid dyshomeostasis became a focus of AD research. Clinically, lipidomic and metabolomic studies have consistently shown alterations in the levels of various lipid classes emerging in early stages of AD brains. Mechanistically, decades of discovery research have revealed multifaceted interactions between lipid metabolism and key AD pathogenic mechanisms including amyloidogenesis, bioenergetic deficit, oxidative stress, neuroinflammation, and myelin degeneration. In the present review, converging evidence defining lipid dyshomeostasis in AD is summarized, followed by discussions on mechanisms by which lipid metabolism contributes to pathogenesis and modifies disease risk. Furthermore, lipid‐targeting therapeutic strategies, and the modification of their efficacy by disease stage, ApoE status, and metabolic and vascular profiles, are reviewed.

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Section: Reducing Lipid Accumulationsmentioning

confidence: 99%

Lipid metabolism and Alzheimer's disease: clinical evidence, mechanistic link and therapeutic promise

Yin

2022

The FEBS Journal

112

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“…l -Carnitine is an amino acid derivative that participates in the transport of long-chain fatty acids into the mitochondria. It improves mitochondrial functions and exerts beneficial effects in neurological disorders ( 49 ). An upregulated lysoPA correlated with the occurrence of several inflammatory conditions, such as asthma ( 50 ), cancer ( 51 ), and autoimmune hepatitis ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

Disturbance of Gut Bacteria and Metabolites Are Associated with Disease Severity and Predict Outcome of NMDAR Encephalitis: A Prospective Case–Control Study

Gong

Liu

et al. 2022

Front. Immunol.

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ObjectiveWe aimed to investigate the associations between the intestinal microbiota, metabolites, cytokines, and clinical severity in anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis and to further determine the predictive value of the intestinal microbiota or metabolites in clinical prognosis.MethodsIn this prospective observational cohort study of 58 NMDAR encephalitis patients and 49 healthy controls, fecal microbiota, metabolites, and cytokines were quantified and characterized by16S rRNA gene sequencing, liquid chromatography–mass spectrometry, and the Luminex assay, respectively.ResultsThere were marked variations in the gut microbiota composition and metabolites in critically ill patients. We identified 8 metabolite modules (mainly characterized by fatty acid, glycerophosphoethanolamines, and glycerophosphocholines) that were distinctly classified as negatively or positively associated with bacterial co-abundance groups (CAGs). These CAGs were mainly composed of Bacteroides, Eubacterium_hallii_group, Anaerostipes, Ruminococcus, Butyricicoccus, and Faecalibacterium, which were substantially altered in patients. In addition, these fecal and serum metabolic modules were further correlated with the serum cytokines. Additionally, the combination of clinical features, microbial marker (Granulicatella), and a panel of metabolic markers could further enhance the performance of prognosis discrimination significantly, which yielded an area under the receiver operating characteristic curve of (AUC) of 0.94 (95%CI = 0.7–0.9). Patients with low bacterial diversity are more likely to develop relapse than those with higher bacterial diversity (log-rank p = 0.04, HR = 2.7, 95%CI = 1.0–7.0).InterpretationThe associations between the multi-omics data suggested that certain bacteria might affect the pathogenesis of NMDAR encephalitis by modulating the metabolic pathways of the host and affecting the production of pro-inflammatory cytokines. Furthermore, the disturbance of fecal bacteria may predict the long-term outcome and relapse in NMDAR encephalitis.

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“…ALC is considered a promising antidepressant, especially for older patients (82,83). Under the action of carnitine acyltransferase in vivo, L-carnitine uses acylcarnitine as a carrier to deliver short-chain acyl groups in the mitochondria to the outer mitochondrial cell membrane, and transfer the long-chain fatty acids outside the membrane to the membrane, so that they can perform β-oxidation in the mitochondrial matrix to produce energy (84,85), and maintain the balance of energy metabolism in the body. The decrease in carnitine content will increase the concentration of acetyl-CoA in the mitochondria.…”

Section: Discussionmentioning

confidence: 99%

Study of Antidepressant-Like Effects of Albiflorin and Paeoniflorin Through Metabolomics From the Perspective of Cancer-Related Depression

et al. 2022

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Mental health has become a new challenge in cancer treatment, with a high prevalence of depression in patients with cancer. Albiflorin (AF) and paeoniflorinn (PF) are isomers extracted from the root of Paeoniae Radix Alba (Baishao in Chinese), belonging to the monoterpene glycosides, and multiple studies have been conducted on their antidepression and anti-cancer effects. However, the effects of AF and PF on cancer-related depression are unclear. Therefore, the current study aims to investigate whether the two isomers are able to exert antidepressant-like effects and understand the underlying mechanisms in a rat model, established by combining irradiation with chronic restraint stress and solitary confinement. Our results demonstrate a significant regulation of AF and PF in the pharmacodynamic index, including the peripheral blood, organ index, behavioral traits, and HPA axis, relative to control rats. In serum and cerebral cortex metabonomics analysis, AF and PF showed a significantly restorative trend in abnormal biomarkers and regulating ether lipid metabolism, alanine, aspartate, glutamate metabolism, tryptophan metabolism, carnitine metabolism, arachidonic acid metabolism, arginine and proline metabolism pathway. Eight potential biomarkers were further screened by means of receiver operating characteristic (ROC) analysis. The data indicate that AF and PF could effectively ameliorate a depression-like state in the model rats, and the mechanism may be associated with the regulation of the neuroendocrine immune system and disrupted metabolic pathways. Further experiments are warranted to comprehensively evaluate the antidepressant effects of AF and PF in cancer-related depression. This study provides a better insight into the action mechanisms of antidepression of TCM, and provides a new perspective for the therapy of cancer-related depression.

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Mechanistic perspectives on differential mitochondrial-based neuroprotective effects of several carnitine forms in Alzheimer’s disease in vitro model

Cited by 16 publications

References 62 publications

Lipid metabolism and Alzheimer's disease: clinical evidence, mechanistic link and therapeutic promise

Lipid metabolism and Alzheimer's disease: clinical evidence, mechanistic link and therapeutic promise

Disturbance of Gut Bacteria and Metabolites Are Associated with Disease Severity and Predict Outcome of NMDAR Encephalitis: A Prospective Case–Control Study

Study of Antidepressant-Like Effects of Albiflorin and Paeoniflorin Through Metabolomics From the Perspective of Cancer-Related Depression

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