There is increasing appreciation among researchers and clinicians of the value of investigating biology and pathobiology at the level of cellular kinase (kinome) activity. Kinome analysis provides valuable opportunity to gain insights into complex biology (including disease pathology), identify biomarkers of critical phenotypes (including disease prognosis and evaluation of therapeutic efficacy), and identify targets for therapeutic intervention through kinase inhibitors. The growing interest in kinome analysis has fueled efforts to develop and optimize technologies that enable characterization of phosphorylation-mediated signaling events in a cost-effective, high-throughput manner. In this review, we highlight recent advances to the central technologies currently available for kinome profiling and offer our perspectives on the key challenges remaining to be addressed.

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Wound healing is a complex process involving intrinsic dermal and epidermal cells, and infiltrating macrophages and leukocytes. Excessive oxidative stress and associated inflammatory processes can impair wound healing, and antioxidants have been reported to improve wound healing in animal models and human subjects. Uric acid (UA) is an efficient free radical scavenger, but has a very low solubility and poor tissue penetrability. We recently developed novel UA analogs with increased solubility and excellent free radical-scavenging properties and demonstrated their ability to protect neural cells against oxidative damage. Here we show that the uric acid analog (6, 8 dithio-UA, but not equimolar concentrations of UA or 1, 7 dimethyl-UA) modified the behaviors of cultured vascular endothelial cells, keratinocytes and fibroblasts in ways consistent with enhancement of the wound healing functions of all three cell types. We further show that 6, 8 dithio-UA significantly accelerates the wound healing process when applied topically (once daily) to full-thickness wounds in mice. Levels of Cu/Zn superoxide dismutase were increased in wound tissue from mice treated with 6, 8 dithio-UA compared to vehicle-treated mice, suggesting that the UA analog enhances endogenous cellular antioxidant defenses. These results support an adverse role for oxidative stress in wound healing and tissue repair, and provide a rationale for the development of UA analogs in the treatment of wounds and for modulation of angiogenesis in other pathological conditions.

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by expanded polyglutamine repeats in the huntingtin (Htt) protein. Mutant Htt may damage and kill striatal neurons by a mechanism involving reduced production of brain-derived neurotrophic factor (BDNF) and increased oxidative and metabolic stress. Because electroconvulsive shock (ECS) can stimulate the production of BDNF and protect neurons against stress, we determined whether ECS treatment would modify the disease process and provide a therapeutic benefit in a mouse model of HD. ECS (50 mA for 0.2 s) or sham treatment was administered once weekly to male N171-82Q Htt mutant mice beginning at 2 months of age. Endpoints measured included motor function, striatal and cortical pathology, and levels of protein chaperones and BDNF. ECS treatment delayed the onset of motor symptoms and body weight loss and extended the survival of HD mice. Striatal neurodegeneration was attenuated and levels of protein chaperones (Hsp70 and Hsp40) and BDNF were elevated in striatal neurons of ECS-treated compared with sham-treated HD mice. Our findings demonstrate that ECS can increase the resistance of neurons to mutant Htt resulting in improved functional outcome and extended survival. The potential of ECS as an intervention in subjects that inherit the mutant Htt gene merits further consideration.

Background Multiple sclerosis (MS) is an inflammatory demyelinating disease featured with neuroinflammation, demyelination, and the loss of oligodendrocytes. Cognitive impairment and depression are common neuropsychiatric symptoms in MS that are poorly managed with the present interventions. Objective This study aimed to investigate the effects of low field magnetic stimulation (LFMS), a novel non‐invasive neuromodulation technology, on cognitive impairment and depressive symptoms associated with MS using a mouse model of demyelination. Methods C57BL female mice were fed with a 0.2% cuprizone diet for 12 weeks to induce a chronic demyelinating model followed by 4 weeks of cuprizone withdrawal with either sham or LFMS treatment. Results Improved cognition and depression‐like behaviour and restored weight gain were observed in mice with LFMS treatment. Immunohistochemical and immunoblotting data showed enhanced myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein expressions (MOG) in the prefrontal cortex of mice with LFMS treatment, supporting that myelin repair was promoted. LFMS also increased the protein expression of mature oligodendrocyte biomarker glutathione‐S‐transferase (GST‐π). In addition, expression of TGF‐β and associated receptors were elevated with LFMS treatment, implicating this pathway in the response. Conclusion Results from the present study revealed LFMS to have neuroprotective effects, suggesting that LFMS has potential therapeutic value for treating cognitive impairment and depression related to demyelination disorders.