The Involvement of Lactosylceramide in Central Nervous System Inflammation Related to Neurodegenerative Disease

Yu, Wen H.; Ying, Jun; Wang, Xifeng; Liu, Xing; Zhao, Tong; Yoon, Sungtae; Zheng, Qingcui; Yang, Fang; Yang, Danying; Hua, Fuzhou

doi:10.3389/fnagi.2021.691230

Cited by 15 publications

(5 citation statements)

References 120 publications

(134 reference statements)

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“…Lactose ceramide (Lactosylceramide, LacCer, CDw17 or Galβ4Glcβ1Cer) is a glycosphingolipid containing a hydrophobic ceramide lipid and a hydrophilic sugar moiety. LacCer, involved in sphinolipid pathway, plays important roles in many diseases, such as neurodegenerative disease, 24 mitochondrial dysfunction in diabetes, 25 hypertrophy 26 and so on. Recently, LacCer was reported to have the potential as biomarker for PCa 27 and could promote cell migration through activation of ERK1/2 28 .…”

Section: Resultsmentioning

confidence: 99%

SIRT2 promotes cell proliferation and migration through mediating ERK1/2 activation and lactosylceramide accumulation in prostate cancer

Lin

Yang

et al. 2022

The Prostate

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Background Prostate cancer (PCa) is an age‐related malignancy with a high incidence and mortality rate due to lack of efficacy drugs for its therapy in late castration‐resistant stage. Sirtuin 2 (SIRT2), a NAD+‐dependent protein deacetylase, is associated with age‐related diseases. However, SIRT2 roles in PCa are unclear yet. Methods Data of SIRT2 expression were extracted from TCGA cohort and GSE54460 cohort. Realtime quantitative PCR and immunohistochemistry were employed to analyze the expression of SIRT2 in PCa tissues. Cell counting Kit‐8 assay, lentiviral transduction, flow cytometry, transwell experiments, western blot and metabolomic analysis were performed to explore the functions of SIRT2. Results SIRT2 exhibited increased expression in castration‐resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC). Overexpression of SIRT2 promoted cell proliferation, the proportion of S phase, migration and invasion, and reduced apoptosis rate. The increased phosphorylated ERK1/2 indicated the regulation of SIRT2 to cell proliferation, migration and invasion through activation of ERK1/2 pathway. Furthermore, SIRT2 affected cell metabolic profile and induces lactosylceramide production through upregulation of B4GALT5, which further contributes cell migration and invasion. Conclusions Our data suggested that SIRT2 is overexpressed in CRPC and NEPC and could promote cell growth and migration through activating ERK1/2 pathway and inducing lactosylceramide production, indicating that SIRT2 has the potential to be a new target for the treatment of PCa.

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Section: Resultsmentioning

confidence: 99%

SIRT2 promotes cell proliferation and migration through mediating ERK1/2 activation and lactosylceramide accumulation in prostate cancer

Lin

Yang

et al. 2022

The Prostate

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“…Some ceramides, including CD17, are significantly elevated in depressed patients [ 47 , 48 , 49 ]. This is important because lactosylcer-amide plays a role in anxiety, neuroinflammation, reduced neurogenesis and neuronal survival, and neurodegenerative processes [ 108 , 109 , 110 ]. Moreover, inflammatory mediators, including TNF-α, activate the synthesis of lactosylcer-amide, which in turn activates ROS and α-type cytosolic phospholipase A 2 (cPLA 2 α), which releases arachidonic acid, another inflammatory mediator [ 111 ].…”

Section: Discussionmentioning

confidence: 99%

Pathway Phenotypes Underpinning Depression, Anxiety, and Chronic Fatigue Symptoms Due to Acute Rheumatoid Arthritis: A Precision Nomothetic Psychiatry Analysis

Smesam

Qazmooz

Khayoon

et al. 2022

JPM

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Rheumatoid arthritis (RA) is a chronic inflammatory and autoimmune disorder which affects the joints in the wrists, fingers, and knees. RA is often associated with depressive and anxiety symptoms as well as chronic fatigue syndrome (CFS)-like symptoms. This paper examines the association between depressive symptoms (measured with the Beck Depression Inventory, BDI), anxiety (Hamilton Anxiety Rating Scale, HAMA), CFS-like (Fibro-fatigue Scale) symptoms and immune–inflammatory, autoimmune, and endogenous opioid system (EOS) markers, and lactosylcer-amide (CD17) in RA. The serum biomarkers were assayed in 118 RA and 50 healthy controls. Results were analyzed using the new precision nomothetic psychiatry approach. We found significant correlations between the BDI, FF, and HAMA scores and severity of RA, as assessed with the DAS28-4, clinical and disease activity indices, the number of tender and swollen joints, and patient and evaluator global assessment scores. Partial least squares analysis showed that 69.7% of the variance in this common core underpinning psychopathology and RA symptoms was explained by immune–inflammatory pathways, rheumatoid factor, anti-citrullinated protein antibodies, CD17, and mu-opioid receptor levels. We constructed a new endophenotype class comprising patients with very high immune–inflammatory markers, CD17, RA, affective and CF-like symptoms, and tobacco use disorder. We extracted a reliable and replicable latent vector (pathway phenotype) from immune data, psychopathology, and RA-severity scales. Depression, anxiety, and CFS-like symptoms due to RA are manifestations of the phenome of RA and are mediated by the effects of the same immune–inflammatory, autoimmune, and other pathways that underpin the pathophysiology of RA.

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“…It is an important inducer of neuroinflammation because it is able to activate astrocytes through phospholipase A2 and RAS/ERK1/2 pathways. Moreover, it is employed for the biosynthesis of gangliosides that are frequently altered in ND [ 127 ]. Patients with PD showed increased levels of hexosylceramide and lactosylceramide [ 95 ], whereas gangliosides GM1 and GM3 have been demonstrated to promote α-synuclein aggregation [ 128 ].…”

Section: From Ceramide Toward Complex Sphingolipidsmentioning

confidence: 99%

Ceramide and Sphingosine-1-Phosphate in Neurodegenerative Disorders and Their Potential Involvement in Therapy

Tringali

Giussani

2022

IJMS

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Neurodegenerative disorders (ND) are progressive diseases of the nervous system, often without resolutive therapy. They are characterized by a progressive impairment and loss of specific brain regions and neuronal populations. Cellular and animal model studies have identified several molecular mechanisms that play an important role in the pathogenesis of ND. Among them are alterations of lipids, in particular sphingolipids, that play a crucial role in neurodegeneration. Overall, during ND, ceramide-dependent pro-apoptotic signalling is promoted, whereas levels of the neuroprotective spingosine-1-phosphate are reduced. Moreover, ND are characterized by alterations of the metabolism of complex sphingolipids. The finding that altered sphingolipid metabolism has a role in ND suggests that its modulation might provide a useful strategy to identify targets for possible therapies. In this review, based on the current literature, we will discuss how bioactive sphingolipids (spingosine-1-phosphate and ceramide) are involved in some ND (Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis) and their possible involvement in therapies.

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The Involvement of Lactosylceramide in Central Nervous System Inflammation Related to Neurodegenerative Disease

Cited by 15 publications

References 120 publications

SIRT2 promotes cell proliferation and migration through mediating ERK1/2 activation and lactosylceramide accumulation in prostate cancer

SIRT2 promotes cell proliferation and migration through mediating ERK1/2 activation and lactosylceramide accumulation in prostate cancer

Pathway Phenotypes Underpinning Depression, Anxiety, and Chronic Fatigue Symptoms Due to Acute Rheumatoid Arthritis: A Precision Nomothetic Psychiatry Analysis

Ceramide and Sphingosine-1-Phosphate in Neurodegenerative Disorders and Their Potential Involvement in Therapy

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