International Journal of Molecular Sciences

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11 pages, 293 KiB

Open AccessEditorial

Uncovering the Lipid Web: Discovering the Multifaceted Roles of Lipids in Human Diseases and Therapeutic Opportunities

by Manoj Kumar Pandey

Int. J. Mol. Sci. 2023, 24(17), 13223; https://doi.org/10.3390/ijms241713223 - 25 Aug 2023

Cited by 1 | Viewed by 928

Abstract

Lipids, characterized by their hydrophobic nature, encompass a wide range of molecules with distinct properties and functions [...] Full article

(This article belongs to the Special Issue The Twist and Turn of Lipids in Human Diseases)

Research

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18 pages, 2525 KiB

Open AccessArticle

Differential Lipidomics, Metabolomics and Immunological Analysis of Alcoholic and Non-Alcoholic Steatohepatitis in Mice

by Erika Dorochow, Nico Kraus, Nicolas Chenaux-Repond, Sandra Pierre, Anja Kolbinger, Gerd Geisslinger, Cristina Ortiz, Christoph Welsch, Jonel Trebicka, Robert Gurke, Lisa Hahnefeld, Sabine Klein and Klaus Scholich

Int. J. Mol. Sci. 2023, 24(12), 10351; https://doi.org/10.3390/ijms241210351 - 19 Jun 2023

Cited by 3 | Viewed by 2385

Abstract

Non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) are the leading causes of liver disease worldwide. To identify disease-specific pathomechanisms, we analyzed the lipidome, metabolome and immune cell recruitment in livers in both diseases. Mice harboring ASH or NASH had comparable disease severities regarding [...] Read more.

Non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) are the leading causes of liver disease worldwide. To identify disease-specific pathomechanisms, we analyzed the lipidome, metabolome and immune cell recruitment in livers in both diseases. Mice harboring ASH or NASH had comparable disease severities regarding mortality rate, neurological behavior, expression of fibrosis marker and albumin levels. Lipid droplet size was higher in NASH than ASH and qualitative differences in the lipidome were mainly based on incorporation of diet-specific fatty acids into triglycerides, phosphatidylcholines and lysophosphatidylcholines. Metabolomic analysis showed downregulated nucleoside levels in both models. Here, the corresponding uremic metabolites were only upregulated in NASH suggesting stronger cellular senescence, which was supported by lower antioxidant levels in NASH as compared to ASH. While altered urea cycle metabolites suggest increased nitric oxide synthesis in both models, in ASH, this depended on increased L-homoarginine levels indicating a cardiovascular response mechanism. Interestingly, only in NASH were the levels of tryptophan and its anti-inflammatory metabolite kynurenine upregulated. Fittingly, high-content immunohistochemistry showed a decreased macrophage recruitment and an increased polarization towards M2-like macrophages in NASH. In conclusion, with comparable disease severity in both models, higher lipid storage, oxidative stress and tryptophan/kynurenine levels were seen in NASH, leading to distinct immune responses. Full article

(This article belongs to the Special Issue The Twist and Turn of Lipids in Human Diseases)

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17 pages, 6205 KiB

Open AccessArticle

Med25 Limits Master Regulators That Govern Adipogenesis

by Jasmine Saunders, Kunal Sikder, Elizabeth Phillips, Anurag Ishwar, David Mothy, Kenneth B. Margulies and Jason C. Choi

Int. J. Mol. Sci. 2023, 24(7), 6155; https://doi.org/10.3390/ijms24076155 - 24 Mar 2023

Cited by 2 | Viewed by 1860

Abstract

Mediator 25 (Med25) is a member of the mediator complex that relays signals from transcription factors to the RNA polymerase II machinery. Multiple transcription factors, particularly those involved in lipid metabolism, utilize the mediator complex, but how Med25 is involved in this context [...] Read more.

Mediator 25 (Med25) is a member of the mediator complex that relays signals from transcription factors to the RNA polymerase II machinery. Multiple transcription factors, particularly those involved in lipid metabolism, utilize the mediator complex, but how Med25 is involved in this context is unclear. We previously identified Med25 in a translatome screen of adult cardiomyocytes (CMs) in a novel cell type-specific model of LMNA cardiomyopathy. In this study, we show that Med25 upregulation is coincident with myocardial lipid accumulation. To ascertain the role of Med25 in lipid accumulation, we utilized iPSC-derived and neonatal CMs to recapitulate the in vivo phenotype by depleting lamins A and C (lamin A/C) in vitro. Although lamin A/C depletion elicits lipid accumulation, this effect appears to be mediated by divergent mechanisms dependent on the CM developmental state. To directly investigate Med25 in lipid accumulation, we induced adipogenesis in Med25-silenced 3T3-L1 preadipocytes and detected enhanced lipid accumulation. Assessment of pertinent mediators driving adipogenesis revealed that C/EBPα and PPARγ are super-induced by Med25 silencing. Our results indicate that Med25 limits adipogenic potential by suppressing the levels of master regulators that govern adipogenesis. Furthermore, we caution the use of early-developmental-stage cardiomyocytes to model adult-stage cells, particularly for dissecting metabolic perturbations emanating from LMNA mutations. Full article

(This article belongs to the Special Issue The Twist and Turn of Lipids in Human Diseases)

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19 pages, 4817 KiB

Open AccessArticle

ACAT1/SOAT1 Blockade Suppresses LPS-Mediated Neuroinflammation by Modulating the Fate of Toll-like Receptor 4 in Microglia

by Haibo Li, Thao N. Huynh, Michael Tran Duong, James G. Gow, Catherine C. Y. Chang and Ta Yuan Chang

Int. J. Mol. Sci. 2023, 24(6), 5616; https://doi.org/10.3390/ijms24065616 - 15 Mar 2023

Cited by 3 | Viewed by 2097

Abstract

Cholesterol is stored as cholesteryl esters by the enzymes acyl-CoA:cholesterol acyltransferases/sterol O:acyltransferases (ACATs/SOATs). ACAT1 blockade (A1B) ameliorates the pro-inflammatory responses of macrophages to lipopolysaccharides (LPS) and cholesterol loading. However, the mediators involved in transmitting the effects of A1B in immune cells is unknown. [...] Read more.

Cholesterol is stored as cholesteryl esters by the enzymes acyl-CoA:cholesterol acyltransferases/sterol O:acyltransferases (ACATs/SOATs). ACAT1 blockade (A1B) ameliorates the pro-inflammatory responses of macrophages to lipopolysaccharides (LPS) and cholesterol loading. However, the mediators involved in transmitting the effects of A1B in immune cells is unknown. Microglial Acat1/Soat1 expression is elevated in many neurodegenerative diseases and in acute neuroinflammation. We evaluated LPS-induced neuroinflammation experiments in control vs. myeloid-specific Acat1/Soat1 knockout mice. We also evaluated LPS-induced neuroinflammation in microglial N9 cells with and without pre-treatment with K-604, a selective ACAT1 inhibitor. Biochemical and microscopy assays were used to monitor the fate of Toll-Like Receptor 4 (TLR4), the receptor at the plasma membrane and the endosomal membrane that mediates pro-inflammatory signaling cascades. In the hippocampus and cortex, results revealed that Acat1/Soat1 inactivation in myeloid cell lineage markedly attenuated LPS-induced activation of pro-inflammatory response genes. Studies in microglial N9 cells showed that pre-incubation with K-604 significantly reduced the LPS-induced pro-inflammatory responses. Further studies showed that K-604 decreased the total TLR4 protein content by increasing TLR4 endocytosis, thus enhancing the trafficking of TLR4 to the lysosomes for degradation. We concluded that A1B alters the intracellular fate of TLR4 and suppresses its pro-inflammatory signaling cascade in response to LPS. Full article

(This article belongs to the Special Issue The Twist and Turn of Lipids in Human Diseases)

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18 pages, 1567 KiB

Open AccessArticle

Acute ACAT1/SOAT1 Blockade Increases MAM Cholesterol and Strengthens ER-Mitochondria Connectivity

by Taylor C. Harned, Radu V. Stan, Ze Cao, Rajarshi Chakrabarti, Henry N. Higgs, Catherine C. Y. Chang and Ta Yuan Chang

Int. J. Mol. Sci. 2023, 24(6), 5525; https://doi.org/10.3390/ijms24065525 - 14 Mar 2023

Cited by 7 | Viewed by 3157

Abstract

Cholesterol is a key component of all mammalian cell membranes. Disruptions in cholesterol metabolism have been observed in the context of various diseases, including neurodegenerative disorders such as Alzheimer’s disease (AD). The genetic and pharmacological blockade of acyl-CoA:cholesterol acyltransferase 1/sterol O-acyltransferase 1 (ACAT1/SOAT1), [...] Read more.

Cholesterol is a key component of all mammalian cell membranes. Disruptions in cholesterol metabolism have been observed in the context of various diseases, including neurodegenerative disorders such as Alzheimer’s disease (AD). The genetic and pharmacological blockade of acyl-CoA:cholesterol acyltransferase 1/sterol O-acyltransferase 1 (ACAT1/SOAT1), a cholesterol storage enzyme found on the endoplasmic reticulum (ER) and enriched at the mitochondria-associated ER membrane (MAM), has been shown to reduce amyloid pathology and rescue cognitive deficits in mouse models of AD. Additionally, blocking ACAT1/SOAT1 activity stimulates autophagy and lysosomal biogenesis; however, the exact molecular connection between the ACAT1/SOAT1 blockade and these observed benefits remain unknown. Here, using biochemical fractionation techniques, we observe cholesterol accumulation at the MAM which leads to ACAT1/SOAT1 enrichment in this domain. MAM proteomics data suggests that ACAT1/SOAT1 inhibition strengthens the ER-mitochondria connection. Confocal and electron microscopy confirms that ACAT1/SOAT1 inhibition increases the number of ER-mitochondria contact sites and strengthens this connection by shortening the distance between these two organelles. This work demonstrates how directly manipulating local cholesterol levels at the MAM can alter inter-organellar contact sites and suggests that cholesterol buildup at the MAM is the impetus behind the therapeutic benefits of ACAT1/SOAT1 inhibition. Full article

(This article belongs to the Special Issue The Twist and Turn of Lipids in Human Diseases)

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13 pages, 2163 KiB

Open AccessArticle

Susceptibility of Fat Tissue to SARS-CoV-2 Infection in Female hACE2 Mouse Model

by Hariprasad Thangavel, Dhanya Dhanyalayam, Kezia Lizardo, Neelam Oswal, Enriko Dolgov, David S. Perlin and Jyothi F. Nagajyothi

Int. J. Mol. Sci. 2023, 24(2), 1314; https://doi.org/10.3390/ijms24021314 - 9 Jan 2023

Cited by 7 | Viewed by 2822

Abstract

The coronavirus disease (COVID-19) is a highly contagious viral illness caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). COVID-19 has had a catastrophic effect globally causing millions of deaths worldwide and causing long-lasting health complications in COVID-19 survivors. Recent studies including ours have [...] Read more.

The coronavirus disease (COVID-19) is a highly contagious viral illness caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). COVID-19 has had a catastrophic effect globally causing millions of deaths worldwide and causing long-lasting health complications in COVID-19 survivors. Recent studies including ours have highlighted that adipose tissue can act as a reservoir where SARS-CoV-2 can persist and cause long-term health problems. Here, we evaluated the effect of SARS-CoV-2 infection on adipose tissue physiology and the pathogenesis of fat loss in a murine COVID-19 model using humanized angiotensin-converting enzyme 2 (hACE2) mice. Since epidemiological studies reported a higher mortality rate of COVID-19 in males than in females, we examined hACE2 mice of both sexes and performed a comparative analysis. Our study revealed for the first time that: (a) viral loads in adipose tissue and the lungs differ between males and females in hACE2 mice; (b) an inverse relationship exists between the viral loads in the lungs and adipose tissue, and it differs between males and females; and (c) CoV-2 infection alters immune signaling and cell death signaling differently in SARS-CoV-2 infected male and female mice. Overall, our data suggest that adipose tissue and loss of fat cells could play important roles in determining susceptibility to CoV-2 infection in a sex-dependent manner. Full article

(This article belongs to the Special Issue The Twist and Turn of Lipids in Human Diseases)

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16 pages, 2510 KiB

Open AccessArticle

Investigation of Plasma-Derived Lipidome Profiles in Experimental Cerebral Malaria in a Mouse Model Study

by Amani M. Batarseh, Fatemeh Vafaee, Elham Hosseini-Beheshti, Azadeh Safarchi, Alex Chen, Amy Cohen, Annette Juillard, Nicholas Henry Hunt, Michael Mariani, Todd Mitchell and Georges Emile Raymond Grau

Int. J. Mol. Sci. 2023, 24(1), 501; https://doi.org/10.3390/ijms24010501 - 28 Dec 2022

Cited by 2 | Viewed by 1900

Abstract

Cerebral malaria (CM), a fatal complication of Plasmodium infection that affects children, especially under the age of five, in sub-Saharan Africa and adults in South-East Asia, results from incompletely understood pathogenetic mechanisms. Increased release of circulating miRNA, proteins, lipids and extracellular vesicles has [...] Read more.

Cerebral malaria (CM), a fatal complication of Plasmodium infection that affects children, especially under the age of five, in sub-Saharan Africa and adults in South-East Asia, results from incompletely understood pathogenetic mechanisms. Increased release of circulating miRNA, proteins, lipids and extracellular vesicles has been found in CM patients and experimental mouse models. We compared lipid profiles derived from the plasma of CBA mice infected with Plasmodium berghei ANKA (PbA), which causes CM, to those from Plasmodium yoelii (Py), which does not. We previously showed that platelet-free plasma (18k fractions enriched from plasma) contains a high number of extracellular vesicles (EVs). Here, we found that this fraction produced at the time of CM differed dramatically from those of non-CM mice, despite identical levels of parasitaemia. Using high-resolution liquid chromatography–mass spectrometry (LCMS), we identified over 300 lipid species within 12 lipid classes. We identified 45 and 75 lipid species, mostly including glycerolipids and phospholipids, with significantly altered concentrations in PbA-infected mice compared to Py-infected and uninfected mice, respectively. Total lysophosphatidylethanolamine (LPE) levels were significantly lower in PbA infection compared to Py infection and controls. These results suggest that experimental CM could be characterised by specific changes in the lipid composition of the 18k fraction containing circulating EVs and can be considered an appropriate model to study the role of lipids in the pathophysiology of CM. Full article

(This article belongs to the Special Issue The Twist and Turn of Lipids in Human Diseases)

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16 pages, 2265 KiB

Open AccessArticle

Low Sulfur Amino Acid, High Polyunsaturated Fatty Acid Diet Inhibits Breast Cancer Growth

by Riccardo Turchi, Flavia Tortolici, Monica Benvenuto, Carolina Punziano, Anastasia De Luca, Stefano Rufini, Raffaella Faraonio, Roberto Bei, Daniele Lettieri-Barbato and Katia Aquilano

Int. J. Mol. Sci. 2023, 24(1), 249; https://doi.org/10.3390/ijms24010249 - 23 Dec 2022

Cited by 4 | Viewed by 2723

Abstract

Cancer cells may acquire resistance to stress signals and reprogram metabolism to meet the energetic demands to support their high proliferation rate and avoid death. Hence, targeting nutrient dependencies of cancer cells has been suggested as a promising anti-cancer strategy. We explored the [...] Read more.

Cancer cells may acquire resistance to stress signals and reprogram metabolism to meet the energetic demands to support their high proliferation rate and avoid death. Hence, targeting nutrient dependencies of cancer cells has been suggested as a promising anti-cancer strategy. We explored the possibility of killing breast cancer (BC) cells by modifying nutrient availability. We used in vitro models of BC (MCF7 and MDA-MB-231) that were maintained with a low amount of sulfur amino acids (SAAs) and a high amount of oxidizable polyunsatured fatty acids (PUFAs). Treatment with anti-apoptotic, anti-ferroptotic and antioxidant drugs were used to determine the modality of cell death. We reproduced these conditions in vivo by feeding BC-bearing mice with a diet poor in proteins and SAAs and rich in PUFAs (LSAA/HPUFA). Western blot analysis, qPCR and histological analyses were used to assess the anti-cancer effects and the molecular pathways involved. We found that BC cells underwent oxidative damage to DNA and proteins and both apoptosis and ferroptosis were induced. Along with caspases-mediated PARP1 cleavage, we found a lowering of the GSH-GPX4 system and an increase of lipid peroxides. A LSAA/HPUFA diet reduced tumor mass and its vascularization and immune cell infiltration, and induced apoptosis and ferroptotic hallmarks. Furthermore, mitochondrial mass was found to be increased, and the buffering of mitochondrial reactive oxygen species limited GPX4 reduction and DNA damage. Our results suggest that administration of custom diets, targeting the dependency of cancer cells on certain nutrients, can represent a promising complementary option for anti-cancer therapy. Full article

(This article belongs to the Special Issue The Twist and Turn of Lipids in Human Diseases)

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18 pages, 1833 KiB

Open AccessArticle

Serum Ceramide Species Are Associated with Liver Cirrhosis and Viral Genotype in Patients with Hepatitis C Infection

by Marcus Höring, Georg Peschel, Jonathan Grimm, Sabrina Krautbauer, Martina Müller, Kilian Weigand, Gerhard Liebisch and Christa Buechler

Int. J. Mol. Sci. 2022, 23(17), 9806; https://doi.org/10.3390/ijms23179806 - 29 Aug 2022

Cited by 8 | Viewed by 1384

Abstract

Hepatitis C virus (HCV) infection affects ceramide metabolism, and, here, we have evaluated associations of eight serum ceramide species with viral load, viral genotype, and disease markers in 178 patients with chronic HCV. In this cohort, ceramide d18:1;O2/16:0 was higher in the serum [...] Read more.

Hepatitis C virus (HCV) infection affects ceramide metabolism, and, here, we have evaluated associations of eight serum ceramide species with viral load, viral genotype, and disease markers in 178 patients with chronic HCV. In this cohort, ceramide d18:1;O2/16:0 was higher in the serum of the 20 diabetic patients compared to the patients without this complication. Moreover, ceramide d18:1;O2/24:0 was negatively correlated with age. Of note, all but ceramide d18:1;O2/16:0 and 26:0 were diminished in the serum of patients with liver cirrhosis and, with the exception of ceramide d18:1;O2/16:0, were negatively correlated with the model for end-stage liver disease (MELD) score. Most of the serum ceramides are carried in low-density lipoprotein (LDL), which rises following effective direct-acting antiviral (DAA) therapy. Ceramide d18:1;O2/24:0 recovered in parallel with LDL, whereas ceramide d18:1;O2/18:0 declined. Genotype-3-infected patients had the lowest ceramide levels, which were comparable to other genotypes after DAA treatment. Notably, ceramide d18:1;O2/23:0 and 24:0 were negatively correlated with the MELD score in patients with liver cirrhosis at the end of DAA therapy. Long-chain (LC) ceramides show adverse effects, whereas very-long-chain (VL) species have protective functions in the liver. The ratio of VL/LC ceramides was higher in non-cirrhosis patients than cirrhosis patients and further increased at the end of therapy in this subgroup. In summary, our study shows that serum ceramide levels are related to liver cirrhosis and viral genotype. Whether the more favorable serum ceramide profile in non-cirrhosis patients, before and after DAA therapy, is of pathophysiological importance needs further investigation. Full article

(This article belongs to the Special Issue The Twist and Turn of Lipids in Human Diseases)

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12 pages, 2252 KiB

Open AccessArticle

Leptin Silencing Attenuates Lipid Accumulation through Sterol Regulatory Element-Binding Protein 1 Inhibition in Nasopharyngeal Carcinoma

by Sheng-Dean Luo, Hsin-Ting Tsai, Tai-Jan Chiu, Shau-Hsuan Li, Ya-Ling Hsu, Li-Jen Su, Meng-Hsiu Tsai, Ching-Yi Lee, Chang-Chun Hsiao and Chang-Han Chen

Int. J. Mol. Sci. 2022, 23(10), 5700; https://doi.org/10.3390/ijms23105700 - 20 May 2022

Cited by 4 | Viewed by 2445

Abstract

Leptin is a crucial regulator of metabolism and energy homeostasis in mammals. Many studies have investigated the impacts of leptin on human cancers, such as proliferation and metastasis. However, the mechanisms underlying leptin-mediated regulation of lipid metabolism in nasopharyngeal carcinoma (NPC) remain incompletely [...] Read more.

Leptin is a crucial regulator of metabolism and energy homeostasis in mammals. Many studies have investigated the impacts of leptin on human cancers, such as proliferation and metastasis. However, the mechanisms underlying leptin-mediated regulation of lipid metabolism in nasopharyngeal carcinoma (NPC) remain incompletely understood. In the current study, leptin downregulation ameliorated lipid accumulation, triglyceride, and cholesterol levels. Mechanistically, diminished leptin by siRNA not only inhibited sterol regulatory element-binding protein 1 (SREBP1), a master regulator of lipid metabolism, at the mRNA and protein levels, but also reduced SREBP1 downstream target expressions, such as fatty acid synthase (FASN) and stearoyl-CoA desaturase-1 (SCD1), in NPC cells. In addition, leptin expression could modulate the promoter activity of SREBP1. We also found that pharmacological inhibition of poly-ADP ribose polymerase-γ (PPAR-γ) resulted in increased SREBP1 expression in leptin-depleted NPC cells. Functionally, SREBP1 overexpression overcame the effects of leptin-silencing attenuated triglyceride level, cholesterol level and cell survival in NPC cells. Taken together, our results demonstrate that leptin is an important regulator of lipid metabolism in NPC cells and might could be a potential therapeutic target for treatment of NPC patients. Full article

(This article belongs to the Special Issue The Twist and Turn of Lipids in Human Diseases)

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Review

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20 pages, 1212 KiB

Open AccessReview

Specialized Proresolving Lipid Mediators: A Potential Therapeutic Target for Atherosclerosis

by Juan Salazar, Daniela Pirela, Manuel Nava, Ana Castro, Lissé Angarita, Heliana Parra, Samuel Durán-Agüero, Diana Marcela Rojas-Gómez, Néstor Galbán, Roberto Añez, Maricarmen Chacín, Andrea Diaz, Nelson Villasmil, Juan Bautista De Sanctis and Valmore Bermúdez

Int. J. Mol. Sci. 2022, 23(6), 3133; https://doi.org/10.3390/ijms23063133 - 15 Mar 2022

Cited by 9 | Viewed by 3375

Abstract

Cardiovascular disease (CVD) is a global public health issue due to its high morbidity, mortality, and economic impact. The implementation of innovative therapeutic alternatives for CVD is urgently required. Specialized proresolving lipid mediators (SPMs) are bioactive compounds derived from ω-3 and ω-6 fatty [...] Read more.

Cardiovascular disease (CVD) is a global public health issue due to its high morbidity, mortality, and economic impact. The implementation of innovative therapeutic alternatives for CVD is urgently required. Specialized proresolving lipid mediators (SPMs) are bioactive compounds derived from ω-3 and ω-6 fatty acids, integrated into four families: Lipoxins, Resolvins, Protectins, and Maresins. SPMs have generated interest in recent years due to their ability to promote the resolution of inflammation associated with the pathogeneses of numerous illnesses, particularly CVD. Several preclinical studies in animal models have evidenced their ability to decrease the progression of atherosclerosis, intimal hyperplasia, and reperfusion injury via diverse mechanisms. Large-scale clinical trials are required to determine the effects of SPMs in humans. This review integrates the currently available knowledge of the therapeutic impact of SPMs in CVD from preclinical and clinical studies, along with the implicated molecular pathways. In vitro results have been promising, and as such, SPMs could soon represent a new therapeutic alternative for CVD. Full article

(This article belongs to the Special Issue The Twist and Turn of Lipids in Human Diseases)

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31 pages, 1724 KiB

Open AccessReview

Fat and Protein Combat Triggers Immunological Weapons of Innate and Adaptive Immune Systems to Launch Neuroinflammation in Parkinson’s Disease

by Shelby Loraine Hatton and Manoj Kumar Pandey

Int. J. Mol. Sci. 2022, 23(3), 1089; https://doi.org/10.3390/ijms23031089 - 19 Jan 2022

Cited by 5 | Viewed by 3116

Abstract

Parkinson’s disease (PD) is the second-most common neurodegenerative disease in the world, affecting up to 10 million people. This disease mainly happens due to the loss of dopaminergic neurons accountable for memory and motor function. Partial glucocerebrosidase enzyme deficiency and the resultant excess [...] Read more.

Parkinson’s disease (PD) is the second-most common neurodegenerative disease in the world, affecting up to 10 million people. This disease mainly happens due to the loss of dopaminergic neurons accountable for memory and motor function. Partial glucocerebrosidase enzyme deficiency and the resultant excess accumulation of glycosphingolipids and alpha-synuclein (α-syn) aggregation have been linked to predominant risk factors that lead to neurodegeneration and memory and motor defects in PD, with known and unknown causes. An increasing body of evidence uncovers the role of several other lipids and their association with α-syn aggregation, which activates the innate and adaptive immune system and sparks brain inflammation in PD. Here, we review the emerging role of a number of lipids, i.e., triglyceride (TG), diglycerides (DG), glycerophosphoethanolamines (GPE), polyunsaturated fatty acids (PUFA), sphingolipids, gangliosides, glycerophospholipids (GPL), and cholesterols, and their connection with α-syn aggregation as well as the induction of innate and adaptive immune reactions that trigger neuroinflammation in PD. Full article

(This article belongs to the Special Issue The Twist and Turn of Lipids in Human Diseases)

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