Brain lipidomics as a rising field in neurodegenerative contexts: Perspectives with Machine Learning approaches

Castellanos, Daniel Baez; Martin-Jimenez, Cynthia; Rojas-Rodríguez, Felipe; Barreto, George E.; González, Janneth

doi:10.1016/j.yfrne.2021.100899

Cited by 41 publications

(32 citation statements)

References 94 publications

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“…Beyond their role in energy mechanisms, lipids are involved in many critical intracellular signaling and transporting processes, as the main component of cellular membranes, which make them a strong candidate for cognition, even in healthy individuals 71 . However, under neurodegenerative conditions characterized by disturbed lipid metabolism, their behavior shifts to become more pro-inflammatory and oxidative, rather than regulatory, and contributes significantly to the acceleration of the neurodegenerative process, as in PD 72 . A good example is the link between lipid dysregulation and alpha-synuclein aggregation, leading to dopaminergic neuronal death in PD 72 .…”

Section: Discussionmentioning

confidence: 99%

“…However, under neurodegenerative conditions characterized by disturbed lipid metabolism, their behavior shifts to become more pro-inflammatory and oxidative, rather than regulatory, and contributes significantly to the acceleration of the neurodegenerative process, as in PD 72 . A good example is the link between lipid dysregulation and alpha-synuclein aggregation, leading to dopaminergic neuronal death in PD 72 .…”

Section: Discussionmentioning

confidence: 99%

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Combined Metabolic Activators Improve Cognitive Functions without Altering Motor Scores in Parkinson’s Disease

Yuluğ¹,

Altay

et al. 2021

Preprint

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The neuropathologic hallmarks of Parkinson's disease (PD) are associated with mitochondrial dysfunction and metabolic abnormalities. We have reported that the Combined Metabolic Activators (CMA), consisting of L-serine, nicotinamide riboside, N-acetyl-L-cysteine, and L-carnitine tartrate can be used in treating metabolic abnormalities. These metabolic activators are the precursors of nicotinamide adenine dinucleotide (NAD+) and glutathione (GSH) and used in activation of mitochondrial and global metabolism. We have performed a placebo-controlled, phase-2 study in Alzheimer's disease (AD) patients and reported that the cognitive functions in AD patients is significantly improved 29% in the CMA group whereas it is improved only 14% in the placebo group after 84 days of CMA administration. Here, we designed a randomized, double-blinded, placebo-controlled, phase-2 study in PD patients with CMA administration. We found that the cognitive functions in PD patients is significantly improved 21% in the CMA group, whereas it is improved only 11% in the placebo group after 84 days of CMA administration. We also found that the administration of CMA did not affect motor functions in PD patients. We performed a comprehensive multi-omics analysis of plasma proteins and metabolites, and revealed the molecular mechanism associated with the treatment of the patients. In conclusion, our results show that treating PD patients with CMAs leads to enhanced cognitive function, as recently reported in AD patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Combined Metabolic Activators Improve Cognitive Functions without Altering Motor Scores in Parkinson’s Disease

Yuluğ¹,

Altay

et al. 2021

Preprint

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“…In the brain, lipids are required for myelination and signal transduction [41]. A dysregulated lipid profile is associated with neurological disorders [42].…”

Section: B Infantis Supplementation Changes Brain Lipidomic Profiles In Wd-fed Micementioning

confidence: 99%

Intestinal Microbiota Remodeling Protects Mice from Western Diet-Induced Brain Inflammation and Cognitive Decline

Jena

Setayesh

Sheng

et al. 2022

Cells

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It has been shown that the Western diet (WD) induces systemic inflammation and cognitive decline. Moreover, probiotic supplementation and antibiotic treatment reduce diet-induced hepatic inflammation. The current study examines whether shaping the gut microbes by Bifidobacterium infantis (B. infantis) supplementation and antibiotic treatment reduce diet-induced brain inflammation and improve neuroplasticity. Furthermore, the significance of bile acid (BA) signaling in regulating brain inflammation was studied. Mice were fed a control diet (CD) or WD for seven months. B. infantis was supplemented to WD-fed mice to study brain inflammation, lipid, metabolomes, and neuroplasticity measured by long-term potentiation (LTP). Broad-spectrum coverage antibiotics and cholestyramine treatments were performed to study the impact of WD-associated gut microbes and BA in brain inflammation. Probiotic B. infantis supplementation inhibited diet-induced brain inflammation by reducing IL6, TNFα, and CD11b levels. B. infantis improved LTP and increased brain PSD95 and BDNF levels, which were reduced due to WD intake. Additionally, B. infantis reduced cecal cholesterol, brain ceramide and enhanced saturated fatty acids. Moreover, antibiotic treatment, as well as cholestyramine, diminished WD-induced brain inflammatory signaling. Our findings support the theory that intestinal microbiota remodeling by B. infantis reduces brain inflammation, activates BA receptor signaling, and improves neuroplasticity.

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“…A conceptual model classifying the different pathways involved in neurodegeneration was developed considering four major models of action [20] (Figure 1). In general, pathways that contribute to neuron survival and degeneration include: (1) intracellular mechanisms such as apoptosis [21], autophagy [22], mitochondrial function, oxidative damage and repair [23], ubiquitin/proteasome [24], (2) local tissue environment such as cell adhesion [25], endocytosis, neurotransmission [26], prions/ transmissible factor [27], (3) systemic environment such as inflammation/immune response [28], lipid/endocrine metabolism [29], brain vasculature [30], (4) and mechanisms related to aging [31], for instance epigenetics [32], neurotrophic factors [33], and telomeres [34]. All these components are highly related and interact with each other to modulate the neurodegenerative process (Figure 2).…”

Section: Main Pathways Involved In Neurological Diseasementioning

confidence: 99%

Punicic Acid and Its Role in the Prevention of Neurological Disorders: A Review

Guerra-Vázquez

Martínez-Ávila

Guajardo‐Flores

et al. 2022

Foods

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Millions of people worldwide are affected by neurodegenerative diseases (NDs). NDs are characterized by progressive damage and death of nerve cells accompanied by high levels of inflammatory biomarkers and oxidative stress conditions. Punicic acid, the main bioactive component of pomegranate (Punica granatum) seed oil, is an omega-5 isomer of conjugated α-linoleic acid that has shown strong anti-oxidative and anti-inflammatory effects that contributes towards its positive effect against a wide arrange of diseases. Punicic acid decreases oxidative damage and inflammation by increasing the expression of peroxisome proliferator-activated receptors. In addition, it can reduce beta-amyloid deposits formation and tau hyperphosphorylation by increasing the expression of GLUT4 protein and the inhibition of calpain hyperactivation. Microencapsulated pomegranate, with high levels of punicic acid, increases antioxidant PON1 activity in HDL. Likewise, encapsulated pomegranate formulations with high levels of punicic acid have shown an increase in the antioxidant PON1 activity in HDL. Because of the limited brain permeability of punicic acid, diverse delivery formulations have been developed to enhance the biological activity of punicic acid in the brain, diminishing neurological disorders symptoms. Punicic acid is an important nutraceutical compound in the prevention and treatment of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s disease.

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Brain lipidomics as a rising field in neurodegenerative contexts: Perspectives with Machine Learning approaches

Cited by 41 publications

References 94 publications

Combined Metabolic Activators Improve Cognitive Functions without Altering Motor Scores in Parkinson’s Disease

Combined Metabolic Activators Improve Cognitive Functions without Altering Motor Scores in Parkinson’s Disease

Intestinal Microbiota Remodeling Protects Mice from Western Diet-Induced Brain Inflammation and Cognitive Decline

Punicic Acid and Its Role in the Prevention of Neurological Disorders: A Review

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