Structural Basis of Splicing Modulation by Antitumor Macrolide Compounds.

SF3B is a multi-protein complex essential for branch site (BS) recognition and selection during pre-mRNA splicing. Several splicing modulators with antitumor activity bind SF3B and thereby modulate splicing. Here we report the crystal structure of a human SF3B core in complex with pladienolide B (PB), a macrocyclic splicing modulator and potent inhibitor of tumor cell proliferation. PB stalls SF3B in an open conformation by acting like a wedge within a hinge, modulating SF3B's transition to the closed conformation needed to form the BS adenosine-binding pocket and stably accommodate the BS/U2 duplex. This work explains the structural basis for the splicing modulation activity of PB and related compounds, and reveals key interactions between SF3B and a common pharmacophore, providing a framework for future structure-based drug design.

The cryo-EM structure of the SF3b spliceosome complex bound to a splicing modulator reveals a pre-mRNA substrate competitive mechanism of action.

Somatic mutations in spliceosome proteins lead to dysregulated RNA splicing and are observed in a variety of cancers. These genetic aberrations may offer a potential intervention point for targeted therapeutics. SF3B1, part of the U2 small nuclear RNP (snRNP), is targeted by splicing modulators, including E7107, the first to enter clinical trials, and, more recently, H3B-8800. Modulating splicing represents a first-in-class opportunity in drug discovery, and elucidating the structural basis for the mode of action opens up new possibilities for structure-based drug design. Here, we present the cryogenic electron microscopy (cryo-EM) structure of the SF3b subcomplex (SF3B1, SF3B3, PHF5A, and SF3B5) bound to E7107 at 3.95 Å. This structure shows that E7107 binds in the branch point adenosine-binding pocket, forming close contacts with key residues that confer resistance upon mutation: SF3B1R1074H and PHF5AY36C The structure suggests a model in which splicing modulators interfere with branch point adenosine recognition and supports a substrate competitive mechanism of action (MOA). Using several related chemical probes, we validate the pose of the compound and support their substrate competitive MOA by comparing their activity against both strong and weak pre-mRNA substrates. Finally, we present functional data and structure-activity relationship (SAR) on the PHF5AR38C mutation that sensitizes cells to some chemical probes but not others. Developing small molecule splicing modulators represents a promising therapeutic approach for a variety of diseases, and this work provides a significant step in enabling structure-based drug design for these elaborate natural products. Importantly, this work also demonstrates that the utilization of cryo-EM in drug discovery is coming of age.

The PI3K-AKT pathway: A plausible therapeutic target in Parkinson's disease.

Parkinson's disease is a common progressive and multifactorial neurodegenerative disease, characterized by the loss of midbrain dopaminergic neurons. Numerous pathological processes including, inflammation, oxidative stress, mitochondrial dysfunction, neurotransmitter imbalance, and apoptosis as well as genetic factors may lead to neuronal degeneration. With the emergence of aging population, the health problem and economic burden caused by PD also increase. Phosphatidylinositol 3-kinases-protein kinase B (PI3K-AKT) signaling pathway regulates signal transduction and biological processes such as cell proliferation, apoptosis and metabolism. According to reports, it regulates neurotoxicity and mediates the survival of neurons. Accumulating evidences indicate that some natural products can play a neuroprotective role by activating PI3K-AKT pathway, providing an effective resource for the discovery of potential therapeutic drugs. The current review provides an overview of the PI3K-AKT signaling pathway and review the relationship between this signaling pathway and PD.

Label-free adaptive optics imaging of human retinal macrophage distribution and dynamics.

Microglia are resident central nervous system macrophages and the first responders to neural injury. Until recently, microglia have been studied only in animal models with exogenous or transgenic labeling. While these studies provided a wealth of information on the delicate balance between neuroprotection and neurotoxicity within which these cells operate, extrapolation to human immune function has remained an open question. Here we examine key characteristics of retinal macrophage cells in live human eyes, both healthy and diseased, with the unique capabilities of our adaptive optics-optical coherence tomography approach and owing to their propitious location above the inner limiting membrane (ILM), allowing direct visualization of cells. Our findings indicate that human ILM macrophage cells may be distributed distinctly, age differently, and have different dynamic characteristics than microglia in other animals. For example, we observed a macular pattern that was sparse centrally and peaked peripherally in healthy human eyes. Moreover, human ILM macrophage density decreased with age (∼2% of cells per year). Our results in glaucomatous eyes also indicate that ILM macrophage cells appear to play an early and regionally specific role of nerve fiber layer phagocytosis in areas of active disease. While we investigate ILM macrophage cells distinct from the larger sample of overall retinal microglia, the ability to visualize macrophage cells without fluorescent labeling in the live human eye represents an important advance for both ophthalmology and neuroscience, which may lead to novel disease biomarkers and new avenues of exploration in disease progression.

Organoamine Templated Multifunctional Hybrid Metal Phosphonate Frameworks: Promising Candidates for Tailoring Electrochemical Behaviors and Size-Selective Efficient Heterogeneous Lewis Acid Catalysis.

The successful discovery of novel multifunctional metal phosphonate framework materials that incorporate newer organoamines and their utilization as a potential electroactive material for energy storage applications (supercapacitors) and as efficient heterogeneous catalysts are the most enduring challenges at present. From this perspective, herein, four new inorganic-organic hybrid zinc organodiphosphonate materials, namely, [C5H14N2]2[Zn6(hedp)4] (I), [C5H14N2]0.5[Zn3(Hhedp) (hedp)]·2H2O (II), [C6H16N2][Zn3(hedp)2] (III), and [C10H24N4][Zn6(Hhedp)2(hedp)2] (IV) (H4hedp = 1-hydroxyethane 1,1-diphosphonic acid), have been synthesized through the introduction of different organoamines and then structurally analyzed using various techniques. The compounds (I-IV) possess a three-dimensional network through alternate connectivity of zinc ions and diphosphonate ligands, as confirmed using single-crystal X-ray diffraction. The investigations of electrochemical charge storage behaviors of the present compounds indicate that compound III exhibits a high specific capacitance of 190 F g-1 (76 C g-1) at 1 A g-1, while compound II shows an excellent cycling stability of 90.11% even after 5000 cycles at 5 A g-1 in the 6 M KOH solution. Further, the present materials have also been utilized as active heterogeneous Lewis acid catalysts in the ketalization reaction. The screening of various substrate scopes during the catalytic process confirms the size-selective heterogeneous catalytic nature of the framework compounds. To our utmost knowledge, such a size-selective heterogeneous Lewis acid catalytic behavior has been observed for the first time in the amine templated inorganic-organic hybrid framework family. Moreover, the excellent size-selective catalytic efficiencies with the d10 metal system and recyclability performances make the compounds (I-IV) more efficient and promising Lewis acid heterogeneous catalysts.

Pumpless, modular, microphysiological systems enabling tunable perfusion for long-term cultivation of endothelialized lumens.

Given the increased recognition of the importance of physiologically relevant microenvironments when designing in vitro assays, microphysiological systems (MPS) that mimic the critical function and structure of tissues and organs have gained considerable attention as alternatives to traditional experimental models. Accordingly, the field is growing rapidly, and some promising MPS are being tested for use in pharmaceutical development and toxicological testing. However, most MPS are complex and require additional infrastructure, which limits their successful translation. Here, we present a pumpless, modular MPS consisting of 1) a resistance module that controls flow rate and 2) a physiologically relevant, three-dimensional blood vessel module. Flow is provided by an attached reservoir tank that feeds fluid into the resistance channel via hydrostatic pressure. The flow rate is controlled by the height of the media in the tank and the resistance channel's dimensions. The flow from the resistance module is streamed into the blood vessel module using a liquid bridge. We utilize optical coherence tomography (OCT) to measure fluid velocity at regions of interest. The endothelial cells cultured in the MPS remain viable for up to 14 days and demonstrate the functional characteristics of the human blood vessels verified by tight junction expression and diffusion assay. Our results show that a modular MPS can simulate a functional endothelium in vitro while simplifying the operation of the MPS. The simplicity of the system allows for modifications to incorporate other microenvironmental components and to build other organ-modeling systems easily.

Construction and validation of UV-C decontamination cabinets for filtering facepiece respirators: comment.

In their September 2020 paper [Appl. Opt.59, 7585 (2020)APOPAI0003-693510.1364/AO.401602], Purschke et al. report UV-C transmittance measurements of N95 filtering facepiece respirators (FFRs), including the 3M 1860, which is one of the most widely used FFRs. We have also measured the transmittance of this FFR in our two separate laboratories with multiple FFR samples, and we have obtained transmittance values similar to one another, but very different from what Purschke et al. reported for two of the four FFR layers.

Suboptimal UVA attenuation by broad spectrum sunscreens under outdoor solar conditions contributes to lifetime UVA burden.

BACKGROUND: Broad spectrum sunscreens with a sun protection factor (SPF) of 15 or greater are indicated to decrease the risk of skin cancer and early skin aging caused by the sun if used as directed with other sun protection measures. To determine whether sunscreen product performance is compromised under solar exposure and to test spectral uniformity of protection across the UVA spectrum, we tested broad spectrum sunscreens with a variety of active pharmaceutical ingredients (APIs) and in a variety of dosage forms. METHODS: A cross-sectional market survey of 32 sunscreen drug products containing either organic or inorganic APIs with SPFs of 15, 30, 50, and 70 was tested. UV doses were delivered via natural sun in Silver Spring, Maryland between June and September of 2017. RESULTS: Of the 32 sunscreen drug products, 6 products failed to meet their broad spectrum claim under solar exposure. Using FDA's new proposal to strengthen sunscreen broad spectrum requirements, spectral uniformity based on the mean sunscreen absorbance of UVA1(340-400 nm)/UV (290-400 nm) indicated that ~40% of sunscreen drug products tested had suboptimal UVA protection. CONCLUSION: US consumers may unknowingly be receiving up to 36% more transmitted UVA when selecting between similarly labeled broad spectrum sunscreen drug products with equivalent SPF values. FDA's new proposal may help decrease consumers' overall lifetime UVA burden. Spectral absorbance data on sunscreen performance can be used to further improve the coupling of broad spectrum protection to a product's SPF value so that consumers have improved proportional increases in UV protection.

3-D printed photoreceptor phantoms for evaluating lateral resolution of adaptive optics imaging systems.

With adaptive optics (AO), optical coherence tomography and scanning laser ophthalmoscopy imaging systems can resolve individual photoreceptor cells in living eyes, due to enhanced lateral spatial resolution. However, no standard test method exists for experimentally quantifying this parameter in ophthalmic AO imagers. Here, we present three-dimensional (3-D) printed phantoms, which enable the measurement of lateral resolution in an anatomically relevant manner. We used two-photon polymerization to fabricate two phantoms, which mimic the mosaic of cone photoreceptor outer segments at multiple retinal eccentricities. With these phantoms, we demonstrated that the resolution of two multimodal AO systems is similar to theoretical predictions, with some intriguing speckle effects.

Application of optical coherence tomography and optical path length method for monitoring corneal thickness and refractive index change during corneal cross-linking.

Corneal cross-linking (CXL) using UVA irradiation with a riboflavin photosensitizer has emerged as a new treatment paradigm for corneal ectatic disorders. The thickness threshold for protection of intraocular structures has often been challenged with ongoing developments, and corneal thinning becomes an important safety concern, especially for patients with thin corneas. In this study with an ex vivo bovine eye model, we monitored corneal thinning and corneal refractive index changes using optical coherence tomography (OCT) integrated with an adaptation of the optical path length method. CXL experiments were performed based on the standard protocol that includes removal of the corneal epithelium to facilitate diffusion of riboflavin into the stroma. The corneal stromal thickness and group refractive index were measured by a 1310 nm Fourier-domain OCT imaging system at three critical points of the procedure: immediately after epithelial removal, after 30 min riboflavin instillation, and after 30 min UVA irradiation with continuing instillation. We found that the refractive index of the bovine cornea changed significantly from epithelial removal to riboflavin instillation and UVA irradiation, increasing from 1.377±0.005 (mean±standard deviation) after de-epithelization to 1.387±0.003 after 30 min instillation and 1.388±0.008 after subsequent irradiation. The corneas also underwent a considerable decrease (10%-20%) in stromal thickness with thinning of 95±29 µm (mean±standard deviation) after riboflavin instillation and a further decrease (∼5%) with thinning of 42±19 µm after UVA irradiation. Our study highlights the importance of corneal thickness monitoring during CXL, especially after riboflavin instillation when the decrease is the largest, to avoid delivering endothelial cytotoxic doses. An increase in refractive index heightens the concern for corneal thinning and the need for careful monitoring as a safety precaution.

Electron-Beam-Lithographed Nanostructures as Reference Materials for Label-Free Scattered-Light Biosensing of Single Filoviruses.

Optical biosensors based on scattered-light measurements are being developed for rapid and label-free detection of single virions captured from body fluids. Highly controlled, stable, and non-biohazardous reference materials producing virus-like signals are valuable tools to calibrate, evaluate, and refine the performance of these new optical biosensing methods. To date, spherical polymer nanoparticles have been the only non-biological reference materials employed with scattered-light biosensing techniques. However, pathogens like filoviruses, including the Ebola virus, are far from spherical and their shape strongly affects scattered-light signals. Using electron beam lithography, we fabricated nanostructures resembling individual filamentous virions attached to a biosensing substrate (silicon wafer overlaid with silicon oxide film) and characterized their dimensions with scanning electron and atomic force microscopes. To assess the relevance of these nanostructures, we compared their signals across the visible spectrum to signals recorded from Ebola virus-like particles which exhibit characteristic filamentous morphology. We demonstrate the highly stable nature of our nanostructures and use them to obtain new insights into the relationship between virion dimensions and scattered-light signal.

Cancer-Associated Mutations Mapped on High-Resolution Structures of the U2AF2 RNA Recognition Motifs.

Acquired point mutations of pre-mRNA splicing factors recur among cancers, leukemias, and related neoplasms. Several studies have established that somatic mutations of a U2AF1 subunit, which normally recognizes 3' splice site junctions, recur among myelodysplastic syndromes. The U2AF2 splicing factor recognizes polypyrimidine signals that precede most 3' splice sites as a heterodimer with U2AF1. In contrast with those of the well-studied U2AF1 subunit, descriptions of cancer-relevant U2AF2 mutations and their structural relationships are lacking. Here, we survey databases of cancer-associated mutations and identify recurring missense mutations in the U2AF2 gene. We determine ultra-high-resolution structures of the U2AF2 RNA recognition motifs (RRM1 and RRM2) at 1.1 Å resolution and map the structural locations of the mutated U2AF2 residues. Comparison with prior, lower-resolution structures of the tandem U2AF2 RRMs in the RNA-bound and apo states reveals clusters of cancer-associated mutations at the U2AF2 RRM-RNA or apo-RRM1-RRM2 interfaces. Although the role of U2AF2 mutations in malignant transformation remains uncertain, our results show that cancer-associated mutations correlate with functionally important surfaces of the U2AF2 splicing factor.

Structure-guided U2AF65 variant improves recognition and splicing of a defective pre-mRNA.

Purine interruptions of polypyrimidine (Py) tract splice site signals contribute to human genetic diseases. The essential splicing factor U2AF(65) normally recognizes a Py tract consensus sequence preceding the major class of 3' splice sites. We found that neurofibromatosis- or retinitis pigmentosa-causing mutations in the 5' regions of Py tracts severely reduce U2AF(65) affinity. Conversely, we identified a preferred binding site of U2AF(65) for purine substitutions in the 3' regions of Py tracts. Based on a comparison of new U2AF(65) structures bound to either A- or G-containing Py tracts with previously identified pyrimidine-containing structures, we expected to find that a D231V amino acid change in U2AF(65) would specify U over other nucleotides. We found that the crystal structure of the U2AF(65)-D231V variant confirms favorable packing between the engineered valine and a target uracil base. The D231V amino acid change restores U2AF(65) affinity for two mutated splice sites that cause human genetic diseases and successfully promotes splicing of a defective retinitis pigmentosa-causing transcript. We conclude that reduced U2AF(65) binding is a molecular consequence of disease-relevant mutations, and that a structure-guided U2AF(65) variant is capable of manipulating gene expression in eukaryotic cells.

U2AF65 adapts to diverse pre-mRNA splice sites through conformational selection of specific and promiscuous RNA recognition motifs.

Degenerate splice site sequences mark the intron boundaries of pre-mRNA transcripts in multicellular eukaryotes. The essential pre-mRNA splicing factor U2AF(65) is faced with the paradoxical tasks of accurately targeting polypyrimidine (Py) tracts preceding 3' splice sites while adapting to both cytidine and uridine nucleotides with nearly equivalent frequencies. To understand how U2AF(65) recognizes degenerate Py tracts, we determined six crystal structures of human U2AF(65) bound to cytidine-containing Py tracts. As deoxy-ribose backbones were required for co-crystallization with these Py tracts, we also determined two baseline structures of U2AF(65) bound to the deoxy-uridine counterparts and compared the original, RNA-bound structure. Local structural changes suggest that the N-terminal RNA recognition motif 1 (RRM1) is more promiscuous for cytosine-containing Py tracts than the C-terminal RRM2. These structural differences between the RRMs were reinforced by the specificities of wild-type and site-directed mutant U2AF(65) for region-dependent cytosine- and uracil-containing RNA sites. Small-angle X-ray scattering analyses further demonstrated that Py tract variations select distinct inter-RRM spacings from a pre-existing ensemble of U2AF(65) conformations. Our results highlight both local and global conformational selection as a means for universal 3' splice site recognition by U2AF(65).

Superior Electrochemical Water Splitting and Energy-Storage Performances of In Situ Fabricated Charge-Separated Metal Organophosphonate Single Crystals.

The design and exploration of advanced materials as a durable multifunctional electrocatalyst toward sustainable energy generation and storage development is the most perdurable challenge in the domain of renewable energy research. Herein, a facile in situ solvothermal approach has been adopted to prepare a methylviologen-regulated crystalline metal phosphonate compound, [C12H14N2][Ni(C11H11N2)(H2hedp)2]2•6H2O (NIT1), (H4hedp = 1-hydroxyethane 1,1-diphosphonic acid) and well characterized by several techniques. The as-prepared NIT1 displays excellent bifunctional electrocatalytic activity with dynamic stability toward oxygen evolution reaction (η10 = 288 mV) and hydrogen evolution reaction (η10 = 228 mV) in alkaline (1.0 M KOH) and acidic mediums (0.5 M H2SO4), respectively. Such a low overpotential and Tafel slope (68 mV/dec for OER; 56 mV/dec for HER) along with long-term durability up to 20 h of NIT1 make it superior to benchmark the electrocatalyst and various nonprecious metal-based catalysts under similar experimental condition. Further, the electrochemical supercapacitor measurements (in three-electrode system) reveal that the NIT1 electrode possesses much higher specific capacity of 187.6 C g-1 at a current density of 2 A g-1 (272 C g-1 at 5 mV s-1) with capacitance retention of 75.2% over 10,000 cycles at 14 A g-1 (Coulombic efficiency > 99%) in 6 M KOH electrolyte medium. Finally for a practical application, an asymmetric supercapacitor device (coin cell) is assembled by NIT1 material. The as-fabricated device delivers the maximum energy density of 39.4 Wh kg-1 at a power density of 450 W kg-1 and achieves a wide voltage window of 1.80 V. Notably, the device endures a remarkable cycle performance with cyclic retention of 92% (Coulombic efficiency > 99%) even after 14,000 charge/discharge cycles at 10 A g-1. Nevertheless, the extraordinary electrochemical activities toward OER and HER as well as the high-performance device fabrication for LED illumination of such a noble metal-free lower-dimensional charge-transfer compound are truly path breaking and would be promising for the development of advanced multifunctional materials.

Compact Linear Flow Phantom Model for Retinal Blood-Flow Evaluation.

Impaired retinal blood flow is associated with ocular diseases such as glaucoma, macular degeneration, and diabetic retinopathy. Among several ocular imaging techniques developed to measure retinal blood flow both invasively and non-invasively, adaptive optics (AO)-enabled scanning laser ophthalmoscopy (AO-SLO) resolves individual red blood cells and provides a high resolution with which to measure flow across retinal microvasculature. However, cross-validation of flow measures remains a challenge owing to instrument and patient-specific variability in each imaging technique. Hence, there is a critical need for a well-controlled clinical flow phantom for standardization and to establish blood-flow measures as clinical biomarkers for early diagnosis. Here, we present the design and validation of a simple, compact, portable, linear flow phantom based on a direct current motor and a conveyor-belt system that provides linear velocity tuning within the retinal microvasculature range (0.5-7 mm/s). The model was evaluated using a sensitive AO-SLO line-scan technique, which showed a <6% standard deviation from the true velocity. Further, a clinical SLO instrument showed a linear correlation with the phantom's true velocity (r2 > 0.997). This model has great potential to calibrate, evaluate, and improve the accuracy of existing clinical imaging systems for retinal blood flow and aid in the diagnosis of ocular diseases with abnormal blood flow.

Quantification of Human Photoreceptor-Retinal Pigment Epithelium Macular Topography with Adaptive Optics-Optical Coherence Tomography.

Photoreceptors (PRs) and retinal pigment epithelial (RPE) cells form a functional unit called the PR-RPE complex. The PR-RPE complex plays a critical role in maintaining retinal homeostasis and function, and the quantification of its structure and topographical arrangement across the macula are important for understanding the etiology, mechanisms, and progression of many retinal diseases. However, the three-dimensional cellular morphology of the PR-RPE complex in living human eyes has not been completely described due to limitations in imaging techniques. We used the cellular resolution and depth-sectioning capabilities of a custom, high-speed Fourier domain mode-locked laser-based adaptive optics-optical coherence tomography (FDML-AO-OCT) platform to characterize human PR-RPE complex topography across the temporal macula from eleven healthy volunteers. With the aid of a deep learning algorithm, key metrics were extracted from the PR-RPE complex of averaged AO-OCT volumes including PR and RPE cell density, PR outer segment length (OSL), and PR/RPE ratio. We found a tight grouping among our cohort for PR density, with a mean (±SD) value of 53,329 (±8106) cells/mm2 at 1° decreasing to 8669 (±737) cells/mm2 at 12°. We observed a power function relationship between eccentricity and both PR density and PR/RPE ratio. We found similar variability in our RPE density measures, with a mean value of 7335 (±681) cells/mm2 at 1° decreasing to 5547 (±356) cells/mm2 at 12°, exhibiting a linear relationship with a negative slope of -123 cells/mm2 per degree. OSL monotonically decreased from 33.3 (±2.4) µm at 1° to 18.0 (±1.8) µm at 12°, following a second-order polynomial relationship. PR/RPE ratio decreased from 7.3 (±0.9) µm at 1° to 1.5 (±0.1) µm at 12°. The normative data from this investigation will help lay a foundation for future studies of retinal pathology.

Dietary, Herbal and Nutritional Interventions for Managing Rheumatoid Arthritis: A Review.

Rheumatoid arthritis (RA) is a systemic, inflammatory disease that affects joints and leads to progressive cartilage and bone deterioration. The susceptibility to RA is determined by genetic and environmental factors. Recently, many efforts have been undertaken to develop natural compounds capable of reducing the symptoms of RA to avoid the negative effects of the current anti-inflammatory drugs. Interestingly, substantial data has revealed that nutritional, and herbal supplements may be effective adjuvants in reducing the symptoms of RA by influencing the pathogenic inflammatory processes. In this context, various kinds of food, phenolic substances, spices like ginger, and turmeric, several vitamins, and probiotics are reported to control the activity of inflammatory molecules implicated in the pathophysiology of RA and therefore, have proved successful in slowing the course of this arthritic illness. Therefore, the goal of this review article is to compile various findings on RA that have revealed illuminating information about the antiinflammatory, antioxidant, analgesic, immunomodulatory, and bone erosion-preventing properties of nutritional, and herbal components. Conclusively, this review concentrates on natural ingredients that may enhance overall well-being, promote health, and lessen the risk of RA.

High Mobility Group Box 1 Protein: A Plausible Therapeutic Molecular Target in Parkinson's disease.

Parkinson's disease (PD) is a widespread neurodegenerative disorder that exerts a broad variety of detrimental effects on people's health. Accumulating evidence suggests that mitochondrial dysfunction, neuroinflammation, α-synuclein aggregation and autophagy dysfunction may all play a role in the development of PD. However, the molecular mechanisms behind these pathophysiological processes remain unknown. Currently, research in PD has focussed on high mobility group box 1 (HMGB1), and different laboratory approaches have shown promising outcomes to some level for blocking HMGB1. Given that HMGB1 regulates mitochondrial dysfunction, participates in neuroinflammation, and modulates autophagy and apoptosis, it is hypothesised that HMGB1 has significance in the onset of PD. In the current review, research targeting multiple roles of HMGB1 in PD pathology was integrated, and the issues that need future attention for targeted therapeutic approaches are mentioned.

Erucic Acid: A Possible Therapeutic Agent for Neurodegenerative Diseases.

Neurodegenerative disorders are among the most common life-threatening disorders among the elderly worldwide and are marked by neuronal death in the brain and spinal cord. Several studies have demonstrated the beneficial role of dietary fatty acids in different brain disorders. This is due to their neurotrophic, antioxidant, and anti-inflammatory properties. Furthermore, extensive evidence shows that an unbalanced intake of certain dietary fatty acids increases the risk of neuropsychiatric diseases. Several research has been done on erucic acid, an ingestible omega-9 fatty acid that is found in Lorenzo's oil. Erucic acid was previously thought to be a natural toxin because of its negative effects on heart muscle function and hepatic steatosis, but it has been discovered that erucic acid is regularly consumed in Asian countries through the consumption of cruciferous vegetables like mustard and rapeseed oil with no evidence of cardiac harm. Erucic acid can also be transformed into nervonic acid, a crucial element of myelin. Therefore, erucic acid may have remyelinating effects, which may be crucial for treating different demyelinating conditions. Also, erucic acid exerts antioxidant and anti-inflammatory effects, suggesting its possible therapeutic role in different neurodegenerative disorders. Considering the fruitful effects of this compound, this article reviews the probable role of erucic acid as a pharmacological agent for treating and managing different neurodegenerative disorders.