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While polyphenolic compounds have many health benefits, the potential development of polyphenols for the prevention/treatment of neurological disorders is largely hindered by their complexity as well as by limited knowledge regarding their bioavailability, metabolism, and bioactivity, especially in the brain. We recently demonstrated that dietary(More)
BACKGROUND Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that affects spinal cord and cortical motor neurons. An increasing amount of evidence suggests that mitochondrial dysfunction contributes to motor neuron death in ALS. Peroxisome proliferator-activated receptor gamma co-activator-1α (PGC-1α) is a principal regulator of(More)
Regulation of cytoskeletal dynamics is essential to neuronal plasticity during development and adulthood. Dysregulation of these mechanisms may contribute to neuropsychiatric and neurodegenerative diseases. The neuronal protein kinase, cyclin-dependent kinase 5 (Cdk5), is involved in multiple aspects of neuronal function, including regulation of(More)
Inflammation is a hallmark of many diseases. Although steroids and cyclooxygenase inhibitors are main anti-inflammatory therapeutical agents, they may cause serious side effects. Therefore, developing non-steroid anti-inflammatory agents is urgently needed. A novel hydrosoluble compound, C12 (2,6-bis(4-(3-(dimethylamino)-propoxy)benzylidene)cyclohexanone),(More)
Prohibitin 1 (PHB1) is a highly conserved protein that is mainly localized to the inner mitochondrial membrane and has been implicated in regulating mitochondrial function in yeast. Because mitochondria are emerging as an important regulator of vascular homeostasis, we examined PHB1 function in endothelial cells. PHB1 is highly expressed in the vascular(More)
As a major intracellular source of reactive oxygen species (ROS), mitochondria are involved in aging and lifespan regulation. Using the yeast chronological aging model, researchers have identified conserved signaling pathways that affect lifespan by modulating mitochondrial functions. Caloric restriction and a genetic mimetic with reduced target of(More)
BACE1 (β-secretase) plays a central role in the β-amyloidogenesis of Alzheimer's disease (AD). The ubiquitin-proteasome system, a major intracellular protein quality control system, has been implicated recently in BACE1 metabolism. We report that the SCF(Fbx2) -E3 ligase is involved in the binding and ubiquitination of BACE1 via its Trp 280 residue of(More)
Intense noise exposure causes hearing loss by inducing degeneration of spiral ganglia neurites that innervate cochlear hair cells. Nicotinamide adenine dinucleotide (NAD(+)) exhibits axon-protective effects in cultured neurons; however, its ability to block degeneration in vivo has been difficult to establish due to its poor cell permeability and serum(More)
The nutrient-sensing target of rapamycin (TOR) pathway appears to have a conserved role in regulating life span. This signaling network is complex, with many downstream physiological outputs, and thus the mechanisms underlying its age-related effects have not been elucidated fully. We demonstrated previously that reduced TOR signaling (intor1Delta strains)(More)
BACKGROUND Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine that regulates inflammatory reactions and the pathophysiology of many inflammatory diseases. Intervertebral disc (IVD) degeneration is characterized by an inflammatory reaction, but the potential role of MIF in IVD degeneration has not been determined. Recent studies have(More)