Lipoxygenases catalyze the peroxidation of fatty acids which contain bisallylic hydrogens between two cis double bonds, such as in linoleic acid (LA) and arachidonic acid (AA). Lipoxygenases are named according to their product specificity with AA as the substrate because AA is the precursor of many active lipid metabolites that are involved in a number of significant disease states. The human genome contains six functional human lipoxygenases (LOX) genes (ALOX5, ALOX12, ALOX12B, ALOX15, ALOX15B, eLOX3) encoding for six different human LOX isoforms (h5-LOX, h12S-LOX, h12R-LOX, h15-LOX-1, h15-LOX-2, eLOX3, respectively). The biological role in health and disease for each LOX isozyme varies dramatically, ranging from asthma to diabetes or stroke. The nomenclature of the LOX isozymes is loosely based on the carbon position (e.g., 5, 12, or 15) at which they oxidize arachidonic acid to form the corresponding hydroperoxyeicosatetraenoic acid (HpETE), which is reduced to the hydroxyeicosatetraenoic acid (HETE) by intracellular glutathione peroxidases. Lipoxygenase inhibitors are difficult to formulate due to challenges with solubility and other factors, therefore new formulations are needed.

Lipoxygenases form a large family of enzymes capable of oxidizing arachidonic acid and related polyunsaturated fatty acids. One such lipoxygenase, 12/15 LOX can oxidize both the C-12 and C-15 of arachidonic acid, forming 12- or 15-hydroperosyarachidonic acid (12- or 15-HPETE). Lipoxygenases and their metabolites have been implicated in many diseases. In particular 12/15-LOX (also known as 15-LOX-1, 15-LOX, or 15-LO-1 in humans and L-12-LoX, leukocyte-type 12-LO, or L-12-LO in mice) plays a role in atherogenesis, diabetes, Alzheimer's, newborn periventricular leukomalacia, breast cancer, and stroke. Whatever the name, the protein is encoded by the gene ALOX15 in both mice and humans. Lox inhibitors are difficult to develop due to the mouse and human homologs having different substrate and inhibitor specificities - 12/15 LOX produces predominantly 15-HETE in humans and 12-HETE in mice. So existing inhibitors are not selective for 12/15 LOX with regard to other LOX isoforms. In addition, many are strong antioxidants and therefore may result in off-target effects. 

Researchers at UC Irvine have developed an organoid culture system capable of generating three-dimensional molecular gradients. This recapitulates in vivo tissue development more accurately than current two-dimensional organoid culture systems and will allow scientists to study human-specific disease mechanisms in native tissue.

During initial stages of development, the human brain self assembles from a vast network of billions of neurons into a system capable of sophisticated cognitive behaviors. The human brain maintains these capabilities over a lifetime of homeostasis, and neuroscience helps us explore the brain’s capabilities. The pace of progress in neuroscience depends on experimental toolkits available to researchers. New tools are required to explore new forms of experiments and to achieve better statistical certainty.Significant challenges remain in modern neuroscience in terms of unifying processes at the macroscopic and microscopic scale. Recently, brain organoids, three-dimensional neural tissue structures generated from human stem cells, are being used to model neural development and connectivity. Organoids are more realistic than two-dimensional cultures, recapitulating the brain, which is inherently three-dimensional. While progress has been made studying large-scale brain patterns or behaviors, as well as understanding the brain at a cellular level, it’s still unclear how smaller neural interactions (e.g., on the order of 10,000 cells) create meaningful cognition. Furthermore, systems for interrogation, observation, and data acquisition for such in vitro cultures, in addition to streaming data online to link with these analysis infrastructures, remains a challenge.

Researchers at the University of California, Riverside (UCR) in collaboration Nationwide Children’s Hospital  have developed and characterized small peptidomimetics that act as EphA4 agonists. Given ALS is a heterogeneous disease, astrocytes reprogrammed from the fibroblasts of patients with sporadic and SOD1-linked ALS (iAstrocytes) were cultured with MNs and the UCR/Nationwide EphA4 agonists.  As seen in Fig. 1, these small agonistic peptidomimetics decrease MN death in iAstrocytes derived from sporadic ALS (sALS) cells.     

Researchers at UC Irvine have discovered a novel mechanism by which restoration of protective nerve coverings fails in degenerative disease like multiple sclerosis. While therapeutics to slow disease progression exist, there are currently none aimed at preventing or restoring damage to nerve coverings.

Stress and loneliness are biologically toxic factors with adverse effects on mental and physical health. The 2018 Gallup World Poll found a 25%–40% increase in stress, worry, and anger in the US from 2008 to 2018. Loneliness is associated with considerable distress, and older adults are vulnerable to loneliness due to losses, physical decline, and social isolation. The COVID-19 pandemic led to increased social isolation, though some older adults with higher levels of resilience and wisdom faced the pandemic with greater fortitude than younger adults.Aging is associated with numerous stressors that negatively impact older adults’ well-being. Resilience improves ability to cope with stressors and can be enhanced in older adults. Senior housing communities are promising settings to deliver positive psychiatry interventions due to rising resident populations and potential impact of delivering interventions directly in the community. 

Manganese (Mn) is an essential metal that must be maintained at levels within a narrow physiological range in cells and organisms to avoid deficiency or toxicity. Humans can be exposed to elevated manganese levels from occupational sources (e.g., welding) or environmental sources (e.g., drinking water). Elevated manganese levels cause manganese to accumulate in the brain, inducing neurotoxicity that can manifest as parkinsonism. Thus, manganese toxicity is a public health concern and developing ways to treat it is crucial. Based on elucidative manganese homeostasis studies, a UC Santa Cruz researcher, in collaboration with researchers at University of Texas at Austin, has developed methods for treating manganese toxicity.

Neuronal injury is the major pathology caused by CNS injuries like stroke or spinal cord injury. However, currently available biomarkers for CNS injuries are either not expressed in neurons at all, or are expressed constitutively in all neurons, regardless of whether the neurons are injured or not. ATF3 as a CNS injury biomarker is revolutionary because its baseline expression in CNS is very low, and it is rapidly induced only in CNS neurons shortly after CNS injuries like stroke or spinal cord injury.  Of note, human serum ATF3 level can be easily measured by a commercially available ELISA kit.

Researchers at the University of California, Davis have developed a method of treating or mitigating seizure, treating epilepsy, as well as a method of reducing the frequency of seizures, using cannabigerol or dihydrocannabigerol and analogs thereof.

Success of deep brain stimulation (DBS) procedures relies heavily on the precise placement of electrodes. However, current options for learning this specialized procedure are limited to observing live cases, listening to audio recordings, or watching computer simulation videos. Researchers at UC Irvine have developed a first-of-its-kind, physical simulation model that allows for easy, convenient, and realistic demonstration of DBS electrode placement to benefit both medical professionals and patients alike.

Researchers from the University of California, Riverside have developed potent monoclonal antibody inhibitors with high MMP-12 selectivity.  These antibodies have applications in pharmaceuticals and biomedical sciences. Specifically, these antibodies may be developed as  therapies for inflammatory and neurological diseases. Fig 1: Inhibitory function of the MMP-12 antibodies LG4, LH6, and LH11 towards cdMMP-12. 

Brief description not available

Microelectrodes are the gold standard for measuring the activity of individual neurons at high temporal resolution in any nervous system region and central to defining the role of neural circuits in controlling behavior. Microelectrode technologies such as the Utah or Michigan arrays, have allowed tracking of distributed neural activity with millisecond precision. However, their large footprint and rigidity lead to tissue damage and inflammation that hamper long-term recordings. State of the art Neuropixel and carbon fiber probes have improved on these previous devices by increasing electrode density and reducing probe dimensions and rigidity. Although these probes have advanced the field of recordings, next-generation devices should enable targeted stimulation in addition to colocalized electrical recordings. Optogenetic techniques enable high-speed modulation of cellular activity through targeted expression and activation of light-sensitive opsins. However, given the strong light scattering and high absorption properties of neural tissue optogenetic interfacing with deep neural circuits typically requires the implantation of large-diameter rigid fibers, which can make this approach more invasive than its electrical counterpart.Approaches to integrating optical and electrical modalities have ranged from adding fiber optics to existing Utah arrays to the Optetrode or other integrated electro-optical coaxial structures. These technologies have shown great promise for simultaneous electrical recordings and optical stimulation in vivo. However, the need to reduce the device footprint to minimize immune responses for long-term recordings is still present.

Researchers at the University of California, Davis have developed an approach to improve drug delivery to tumors and metastases in the brain. Their multi-barrier tackling delivery strategy has worked to efficiently impact brain tumor management while also achieving increased survival times in anti-cancer efficacy.

Brief description not available

Brief description not available

Brief description not available

As an important tool for electrophysiological recordings, neural electrodes implanted on the brain surface have been instrumental in basic neuroscience research to study large-scale neural dynamics in various cognitive processes, such as sensorimotor processing as well as learning and memory. In clinical settings, neural recordings have been adopted as a standard tool to monitor the brain activity in epilepsy patients before surgery for detection and localization of epileptogenic zones initiating seizures and functional cortical mapping. Neural activity recorded from the brain surface exhibits rich information content about the collective neural activities reflecting the cognitive states and brain functions. For the interpretation of surface potentials in terms of their neural correlates, most research has focused on local neural activities.   From basic neuroscience research to clinical treatments and neural engineering, electrocorticography (ECoG) has been widely used to record surface potentials to evaluate brain function and develop neuroprosthetic devices. However, the requirement of invasive surgeries for implanting ECoG arrays significantly limits the coverage of different cortical regions, preventing simultaneous recordings from spatially distributed cortical networks. However, this rich information content of surface potentials encoded for the large-scale cortical activity remains unexploited and little is known on how local surface potentials are correlated with the spontaneous neural activities of distributed large-scale cortical networks. Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin-top:0in; mso-para-margin-right:0in; mso-para-margin-bottom:8.0pt; mso-para-margin-left:0in; line-height:107%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

Microelectrodes are the gold standard for measuring the activity of individual neurons at high temporal resolution in any nervous system region and central to defining the role of neural circuits in controlling behavior.Microelectrode technologies such as the Utah or Michigan arrays, have allowed tracking of distributed neural activity with millisecond precision. However, their large footprint and rigidity lead to tissue damage and inflammation that hamper long-term recordings. State of the art Neuropixel and carbon fiber probes have improved on these previous devices by increasing electrode density and reducing probe dimensions and rigidity.Although these probes have advanced the field of recordings, next-generation devices should enable targeted stimulation in addition to colocalized electrical recordings. Optogenetic techniques enable high-speed modulation of cellular activity through targeted expression and activation of light-sensitive opsins. However, given the strong light scattering and high absorption properties of neural tissue optogenetic interfacing with deep neural circuits typically requires the implantation of large-diameter rigid fibers, which can make this approach more invasive than its electrical counterpart.Approaches to integrating optical and electrical modalities have ranged from adding fiber optics to existing Utah arrays to the Optetrode or other integrated electro-optical coaxial structures. These technologies have shown great promise for simultaneous electrical recordings and optical stimulation in vivo. However, the need to reduce the device footprint to minimize immune responses for long-term recordings is still present.

Prof. Seema K. Tiwari-Woodruff from the University of California, Riverside, Prof. John Katzellenbogen and colleagues from the University of Illinois have developed novel estrogen receptor β (ERβ) drugs for the treatment of MS. These novel MS drugs are specific for ERβ and have tremendous potential for the treatment of MS as well as other neurodegenerative diseases. In general, estrogens have anti-inflammatory and neuroprotective activities and clinically reduce the severity of MS and other neurodegenerative diseases. The compounds are more superior to other estrogenic drugs due to their specificity for ERβ and lack of undesirable effects such as feminization and increased risk of cancer. Fig 1: Therapeutic treatment with the UCR ERβ ligands began at peak disease (day 17) and was continued daily till day 36. ERβ ligands (blue, and orange) significantly attenuated clinical disease severity compared to vehicle treatment (red).  

Dural tear is a frequent and costly complication of spinal surgery, which can cause cerebrospinal fluid (CSF) leakage, triggering additional, serious post-operative difficulties. Researchers at UC Irvine have developed a new method and device to mitigate dural tears in a rapid, safe, and water-tight manner

Researchers at the University of California, Davis have developed small molecule inhibitors for use in treating drug-resistant tumors – including cancerous tumors.

UCLA researchers in the Department of Psychology have developed a behavioral training program for the improvement of anhedonia.

Researchers at the University of California, Davis have developed a method of synthesizing stem cell-derived, exosome-mimicking, nanovesicles that have the therapeutic potential to rescue apoptotic neurons in culture.