Activating AMPK or inactivating calcineurin slows ageing in Caenorhabditis elegans and both have been implicated as therapeutic targets for age-related pathology in mammals. However, the direct targets that mediate their effects on longevity remain unclear. In mammals, CREB-regulated transcriptional coactivators (CRTCs) are a family of cofactors involved in diverse physiological processes including energy homeostasis, cancer and endoplasmic reticulum stress.
The Journal of Neuroscience: The Official Journal of the Society for Neuroscience
Spinal muscular atrophy (SMA), a recessive neurodegenerative disease, is characterized by the selective loss of spinal motor neurons. No available therapy exists for SMA, which represents one of the leading genetic causes of death in childhood. SMA is caused by a mutation of the survival-of-motor-neuron 1 (SMN1) gene, leading to a quantitative defect in the survival-motor-neuron (SMN) protein expression. All patients retain one or more copies of the SMN2 gene, which modulates the disease severity by producing a small amount of stable SMN protein.
Forkhead box O (FOXO) transcription factors control diverse cellular functions, such as cell death, metabolism, and longevity. We analyzed FOXO3/FKHRL1 expression and subcellular localization in tumor sections of neuroblastoma patients and observed a correlation between nuclear FOXO3 and high caspase-8 expression. In neuroblastoma caspase-8 is frequently silenced by DNA methylation. Conditional FOXO3 activated caspase-8 gene expression but did not change the DNA-methylation pattern of regulatory sequences in the caspase-8 gene.
Alcohol use and abuse appear to be related to neuroadaptive changes at functional, neurochemical, and structural levels. Acute and chronic ethanol exposure have been shown to modulate function of the activity-dependent gene transcription factor, cAMP-responsive element binding (CREB) protein in the brain, which may be associated with the development of alcoholism.
The dynorphin/?-opioid receptor system has been implicated in the pathogenesis and pathophysiology of several psychiatric disorders. In the present review, we present evidence indicating a key role for this system in modulating neurotransmission in brain circuits that subserve mood, motivation, and cognitive function.
RATIONALE: The transcription factor cAMP responsive element-binding protein 1 (CREB1) has a complex influence on behavioural responses to drugs of abuse which varies depending on the brain region in which it is expressed. In response to drug exposure, CREB1 is phosphorylated in the striatum, a structure that is critically involved in reward-related learning. OBJECTIVE: The present study assessed the role of striatal CREB1 and its coactivator CREB-binding protein (CBP) in behavioural responses to psychostimulants.
Aging is characterized by development of diseases and cancer due to loss of central and peripheral neuroendocrine-immune responses. Free radicals exert deleterious effects on neural-immune functions in the brain, heart, and lymphoid organs and thus, affecting the health. Bacopa monnieri (brahmi), an Ayurvedic herb, and L-deprenyl, a monoamine oxidase-B inhibitor, have been widely used in the treatment of neurodegenerative diseases.
Arteriosclerosis, Thrombosis, and Vascular Biology
OBJECTIVE: C-Reactive protein (CRP), a cardiovascular risk marker, could also participate in atherosclerosis. Atherosclerotic plaques express CRP and interleukin (IL)-10, a major antiinflammatory cytokine. IL-10 deficiency results in increased lesion formation, whereas IL-10 delivery attenuates lesions. We tested the effect of CRP on lipopolysaccharide (LPS)-induced IL-10 secretion in human monocyte-derived macrophages (HMDMs).
FASEB journal: official publication of the Federation of American Societies for Experimental Biology
Standardized Ginkgo biloba extract EGb 761 exhibits beneficial effects to patients with Alzheimer's disease (AD). It was previously demonstrated that EGb 761 inhibits amyloid beta (Abeta) oligomerization in vitro, protects neuronal cells against Abeta toxicity, and improves cognitive defects in a mouse model of AD (Tg 2576). In this study, the neurogenic potential of EGb 761 and its effect on cAMP response element binding protein (CREB) were examined in a double transgenic mouse model (TgAPP/PS1).
Increasing evidence suggests that depression may be both a cause and consequence of neurological disorders such as Alzheimer's disease (AD), and that anti-depressants could provide an alternative strategy to current AD therapies. Association of side effect and herbal-drug interaction with conventional anti-depressant and St. John's wort warrant investigating new anti-depressant drugs. Anti-depressant effects of ginkgo biloba extract (EGb 761) have been demonstrated in animal models of depression and in human volunteers.