Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human 5-HT(6) receptor (5-HT(6)R) is one of the latest cloned receptors among the known 5-HT receptors. Its abundant distribution in the limbic region, which participates in the control of mood and emotion and is involved in nervous system diseases such as depression and Alzheimer disease, has caused it to generate much interest. However, the cellular mechanisms of 5-HT(6)R are poorly understood. In the present study we found, using a yeast two-hybrid assay, that the carboxyl-terminal region of 5-HT(6)R interacts with the Fyn-tyrosine kinase. We also determined using a glutathione S-transferase pulldown assay that this interaction was mediated through the SH3 domain of Fyn and confirmed this by co-immunoprecipitation assays in two different transfected cell lines as well as in adult rat brains. Immunocyto(histo)chemistry also showed prominent co-localization between 5-HT(6)R and Fyn in transfected cells and a similar distribution between 5-HT(6)R and Fyn in the rat brain. Based on this interaction, we further examined the modulation of 5-HT(6)R by Fyn and vice versa. In addition, we demonstrated that the activation of 5-HT(6)R activated the extracellular signal-regulated kinase1/2 via an Fyn-dependent pathway. These findings suggest that Fyn may play an important role in 5-HT(6)R- mediated signaling pathways in the central nervous system.
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PMID:The novel cellular mechanism of human 5-HT6 receptor through an interaction with Fyn. 1718 69

Metabolic alterations are a key player involved in the onset of Alzheimer disease pathophysiology and, in this review, we focus on diet, metabolic rate, and neuronal size differences that have all been shown to play etiological and pathological roles in Alzheimer disease. Specifically, one of the earliest manifestations of brain metabolic depression in these patients is a sustained high caloric intake meaning that general diet is an important factor to take in account. Moreover, atrophy in the vasculature and a reduced glucose transporter activity for the vessels is also a common feature in Alzheimer disease. Finally, the overall size of neurons is larger in cases of Alzheimer disease than that of age-matched controls and, in individuals with Alzheimer disease, neuronal size inversely correlates with disease duration and positively associates with oxidative stress. Overall, clarifying cellular and molecular manifestations involved in metabolic alterations may contribute to a better understanding of early Alzheimer disease pathophysiology.
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PMID:Indices of metabolic dysfunction and oxidative stress. 1734 8

Neurosteroids are steroid structure hormones with neuroactive function. Neurosteroids have rapid, non-genomic actions in CNS. Non-conjugated metabolites of progesterone such as allopregnanolone, are potent positive modulators of GABAA receptors. They open ion channels for Cl- with analgetic, hypnotic, anxiolytic and anticonvulsant effects. By sulphatation the modulation on GABAA receptors is changed to negative with opposite effect. 19-C-steroids as dehydroepiandrosterone and its sulphate are negative modulators of GABAA receptors acting as an excitant and proconvulsant. They are able to modulate positively N-methyl-D-aspartate (NMDA) receptors and open ion canals for Ca2+. Changed (lowered) neurosteroid levels can be involved in many pathological processes as premenstrual syndrome, stress, depression, some forms of epilepsy, Alzheimer disease etc. Future study targeted on regulation of their production and metabolism and understanding of the mechanism of their actions will help to use them therapeutically.
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PMID:[Neurosteroids and their function]. 1741 4

Psychotic symptoms in Alzheimer disease (AD + P) identify a heritable phenotype associated with a more severe course. We recently found an association of AD + P with depression symptom severity. Reports have shown an association of a serotonin-2A receptor (HTR2A) gene T102C polymorphism with AD + P and with depression during AD. We examined the interaction of this common genetic polymorphism with depression and increased psychosis risk. Subjects with possible or probable AD or mild cognitive impairment (MCI) without psychosis at study entry were genotyped for the HTR2A T102C polymorphism and reassessed every 6 months until psychosis onset. Psychotic and depressive symptoms were rated using the CERAD behavioral rating scale (CBRS). Cox proportional hazard models with time-dependent covariates were used to examine associations with psychosis onset. A total of 324 Caucasian subjects completed at least one follow-up exam. Depressive symptom severity was a strong predictor of psychosis onset. Neither psychosis onset nor depression severity was associated with the HTR2A genotype. Genotype interacted with depression severity to moderate the risk of AD + P onset. This did not result from an interaction of HTR2A genotype with antidepressant use. Psychosis onset in AD is strongly associated with severity of depressive symptoms, an association that may be modified by HTR2A genotype.
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PMID:Prediction of psychosis onset in Alzheimer disease: the role of depression symptom severity and the HTR2A T102C polymorphism. 1752 76

Psychiatric disorders are common in Parkinson's disease (PD) and hallucinations are observed in nearly 40% of PD patients. The involvement of dopaminergic system in the pathogenesis of psychosis has been sustained by most of the authors even if several evidences indicate that multiple neurochemical substrates might underlie psychosis in PD. In PD there is an extensive loss of serotoninergic raphe neurons and serotonin dysfunction had been implicated in the pathogenesis of many psychiatric disorders such as depression, schizophrenia, and in psychosis of patients with Alzheimer disease. The association of a serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the 5-HT2A receptor T102C polymorphism with psychosis in a group of patients with PD was investigated. No significant differences in the distribution of allele and genotype frequencies of the 5-HTTLPR (p>0.01) and 5-HT2A T102C (p>0.05) were found between patients and controls as well as between the patients' subgroups without and with psychosis. These data might suggest that 5-HTTLPR and 5-HT2A polymorphisms are not major susceptibility factors of psychotic symptoms in PD patients.
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PMID:Visual hallucinations in Parkinson's disease are not influenced by polymorphisms of serotonin 5-HT2A receptor and transporter genes. 1761 96

The number of people over the age of 60 years with lifelong developmental delays is predicted to double by 2030. Down syndrome (DS) is the most frequent chromosomal cause of developmental delays. As the life expectancy of people with DS increases, changes in body function and structure secondary to aging have the potential to lead to activity limitations and participation restrictions for this population. The purpose of this update is to: (1) provide an overview of the common body function and structure changes that occur in adults with DS as they age (thyroid dysfunction, cardiovascular disorders, obesity, musculoskeletal disorders, Alzheimer disease, depression) and (2) apply current research on exercise to the prevention of activity limitations and participation restrictions. As individuals with DS age, a shift in emphasis from disability prevention to the prevention of conditions that lead to activity and participation limitations must occur. Exercise programs appear to have potential to positively affect the overall health of adults with DS, thereby increasing the quality of life and years of healthy life for these individuals.
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PMID:Aging and Down syndrome: implications for physical therapy. 1771 35

Despite the critical roles of the amyloid precursor protein (APP) in Alzheimer's disease pathogenesis, its physiological function remains poorly established. Our previous studies implicated a structural and functional activity of the APP family of proteins in the developing neuromuscular junction (NMJ). Here we performed comprehensive analyses of neurotransmission in mature neuromuscular synapse of APP deficient mice. We found that APP deletion led to reduced paired-pulse facilitation and increased depression of synaptic transmission with repetitive stimulation. Readily releasable pool size and total releasable vesicles were not affected, but probability of release was significantly increased. Strikingly, the amount of asynchronous release, a measure sensitive to presynaptic calcium concentration, was dramatically increased, and pharmacological studies revealed that it was attributed to aberrant activation of N- and L-type Ca(2+) channels. We propose that APP modulates synaptic transmission at the NMJ by ensuring proper Ca(2+) channel function.
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PMID:Increased asynchronous release and aberrant calcium channel activation in amyloid precursor protein deficient neuromuscular synapses. 1791 26

Recent advances in cognitive neuroscience methods reveal the potential of neuroimaging as be a useful tool in clinical and educational practice. In this review, we review the literature and provide evidence that functional and structural neuroimaging can detect changes with treatment. Further, we show promising initial results showing that the addition of neuroimaging measures can enhance conventional methods to predict outcome and prognosis. Examples are drawn from disorders such as attention-deficit / hyperactivity disorder (ADHD), depression, schizophrenia, obsessive-compulsive disorder (OCD), temporal lobe epilepsy, Alzheimer disease and developmental dyslexia. This evidence raises the intriguing possibility of utilizing neuroimaging data as a critical component in assessing and predicting cognitive abilities and
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PMID:[Contribution of neuroimaging in the prediction of outcome in neuropsychiatric disorders and learning disabilities]. 1796 62

Dysregulation of brain iron homeostasis is central to early neuropathological events in Alzheimer's disease (AD), including oxidative stress, inflammatory processes, amyloid deposition, tau phosphorylation, and neuronal cell cycle regulatory failure, leading to apoptosis. Also, there is a direct link between iron metabolism and AD pathogenesis, demonstrated by the presence of an iron-responsive element in the 5' UTR of the amyloid precursor protein transcript. As a consequence of these findings, a new paradigm is emerging that includes the development of iron-chelating neuroprotective-neurorescue drugs with multimodal functions, acting at various pathological brain targets. This concept is challenging the widely held assumption that "silver bullet" agents are superior to "dirty drugs" in drug therapy for neurodegenerative diseases. At best, the so-called magic bullets exhibit moderate symptomatic activity without modifying the course of disease progression. The present review elaborates on conventional and novel therapeutic targets of various multifunctional iron-chelating drugs (e.g., chemically designed compounds; natural polyphenols) that address multiple central nervous system etiologies in AD, aimed at preventing or slowing disease evolution. A similar approach in drug design is being investigated for treatment of cancer, AIDS, cardiovascular diseases, and depression.
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PMID:Targeting multiple Alzheimer's disease etiologies with multimodal neuroprotective and neurorestorative iron chelators. 1804 80

Vitamin A is necessary for normal embryonic development, but its role in the adult brain is poorly understood. Vitamin A derivatives, retinoids, are involved in a complex signaling pathway that regulates gene expression and, in the central nervous system, controls neuronal differentiation and neural tube patterning. Although a major functional implication of retinoic signaling has been repeatedly suggested in synaptic plasticity, learning and memory, sleep, schizophrenia, depression, Parkinson disease, and Alzheimer disease, the targets and the underlying mechanisms in the adult brain remain elusive.
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PMID:Functional implication of the vitamin A signaling pathway in the brain. 1807 Oct 33


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