Abstract：
:Gamma-secretase (GS) is an enzyme complex that cleaves numerous substrates, and it is best known for cleaving amyloid precursor protein (APP) to form amyloid-beta (Aβ) peptides. Aberrant cleavage of APP can lead to Alzheimer's disease, so much research has been done to better understand GS structure and function in hopes of developing therapeutics for Alzheimer's. Therefore, most of the attention in this field has been focused on developing modulators that reduce pathogenic forms of Aβ while leaving Notch and other GS substrates intact, but GS provides multiple avenues of modulation that could improve AD pathology. GS has complex regulation, through its essential subunits and other associated proteins, providing other targets for AD drugs. Therapeutics can also alter GS trafficking and thereby improve cognition, or move beyond Aβ entirely, effecting Notch and neural stem cells. GS also cleaves substrates that affect synaptic morphology and function, presenting another window by which GS modulation could improve AD pathology. Taken together, GS presents a unique cross road for neural processes and an ideal target for AD therapeutics.
journal_name
Brain Res Bulljournal_title
Brain research bulletinauthors
Carroll CM,Li YMdoi
10.1016/j.brainresbull.2016.04.019subject
Has Abstractpub_date
2016-09-01 00:00:00pages
199-206issue
Pt 2eissn
0361-9230issn
1873-2747pii
S0361-9230(16)30095-8journal_volume
126pub_type
杂志文章,评审abstract：:Saturation and competition binding studies showed that the turtle brain contains sigma sites labeled by both [3H]di-o-tolylguanidine (DTG) and [3H](+)-pentazocine. There was a significant correlation between the IC50 values of sigma ligands for [3H]DTG sites in the turtle vs. rat brain, suggesting that the sites are c...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/s0361-9230(99)00029-5
更新日期：1999-03-15 00:00:00
abstract：:Under standard laboratory conditions rats given access to three separate macronutrient sources compose a diet yielding 31% of their total daily calories as protein, 34% as carbohydrate, and 34% as fat. This selection pattern is dramatically altered with restored access following a 48 h fast. During the first hour of r...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/0361-9230(93)90305-u
更新日期：1993-01-01 00:00:00
abstract：:The effects of changes in ambient and central temperature, amines, PGEu and pyrogen were investigated with respect to the mechanism of Na+-Ca++ ratio in the posterior hypothalamus of the unrestrained cat. Guide tubes were implanted bilaterally above the posterior hypothalamic area of 23 cats so as to accommodate push-...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/0361-9230(76)90102-7
更新日期：1976-05-01 00:00:00
abstract：:The presence of glial cell line-derived neurotrophic factor (GDNF) is described within specific regions of the adult rat pituitary gland. Immune staining methods revealed a small number of GDNF-immunopositive cells in the anterior lobe, and in areas of the neural lobe, while no immunoreactive endocrine cells were obse...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/s0361-9230(00)00242-2
更新日期：2000-05-15 00:00:00
abstract：:The electroencephalographic (EEG) activity of the hippocampus was examined in adult freely moving rats that had had all of the neocortex, including the cingulate cortex and cingulum, removed at birth. Both the cholinergic and serotonergic forms of rhythmical slow activity (RSA or theta) were present in the dorsal hipp...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/0361-9230(91)90017-e
更新日期：1991-03-01 00:00:00
abstract：:Efferent projections from the basal forebrain to the cat's cerebral cortex were traced with the retrograde horseradish peroxidase technique. Different areas of the cerebral cortex of 51 cats were injected with small amounts of horseradish peroxidase. The entire basal forebrain was screened for labeled neurons. Followi...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/0361-9230(84)90165-5
更新日期：1984-05-01 00:00:00
abstract：:Isoflurane (ISO) is an anesthesia and can result in neuron injury. A previous study has indicated that microRNA-302b-3p (miR-302b-3p) exerts a crucial function in modulating cerebral ischemia/reperfusion damage-induced neuronal injury. We sought to examine the role of miR-302b-3p in ISO-induced neuronal injury. In the...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/j.brainresbull.2020.12.016
更新日期：2020-12-25 00:00:00
abstract：:Rats were tested for intracranial self-stimulation (ICSS) via bipolar electrodes situated throughout the thalamus. Of 112 animals in the study, 55 met the criteria for ICSS, with scores ranging from 55 to 921 bar-presses in a 15 minute session. A map of both positive and neutral placements is presented. Positive sites...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/0361-9230(82)90072-7
更新日期：1982-04-01 00:00:00
abstract：:Polymerase chain reaction assays are a powerful tool for detecting the presence of infectious genomes in the cerebrospinal fluid. Positive results always mean a current or pending infection of the central nervous system. Subacute (>7 days) or chronic infections induce an intrathecal humoral immune response and the app...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/s0361-9230(03)00093-5
更新日期：2003-08-15 00:00:00
abstract：:The regeneration of brain tissue remains one of the greatest unsolved challenges in medicine and by many is considered unfeasible. Indeed, the adult mammalian brain does not regenerate tissue, but there is ongoing endogenous neurogenesis, which is upregulated after injury and contributes to tissue repair. This endogen...
journal_title：Brain research bulletin
pub_type： 杂志文章,评审
doi：10.1016/j.brainresbull.2019.05.013
更新日期：2019-08-01 00:00:00
abstract：:Electrophysiologic response characteristics of mouse sciatic nerve and spinal cord were investigated following CNS infection with the temperature-sensitive (ts) vesicular stomatitis virus (VSV) mutant G31 KS5. Measurements were obtained before clinical symptoms of the virus-induced CNS disease appeared. Sciatic nerve ...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/0361-9230(94)90001-9
更新日期：1994-01-01 00:00:00
abstract：:The role of the serotonergic transmission on the negative feedback of corticosterone on the pituitary-adrenal (PA) axis was studied in adult male rats. Animals were given p-chlorophenylalanine (PCPA) and 24 h later were administered corticosterone, 2 h before being subjected to 20 min of noise stress. The main results...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/0361-9230(92)90212-g
更新日期：1992-06-01 00:00:00
abstract：:Mammals and birds are the only animals that exhibit high-amplitude slow-waves (SWs) in the electroencephalogram during sleep. The SWs that characterize slow-wave sleep (SWS) in mammals and birds reflect the large-scale synchronization of slow neuronal activity. In mammals, this synchronization is dependent upon the hi...
journal_title：Brain research bulletin
pub_type： 评论,杂志文章
doi：10.1016/j.brainresbull.2007.02.010
更新日期：2007-05-30 00:00:00
abstract：:Cats pretreated with morphine (5 mg/kg, IP) received naloxone into the area of the locus coeruleus (LC) or the area of the substantia nigra (SN). The LC-treated animals stopped the morphine-induced stereotyped behavior and showed normal but hyperactive behavior. The SN-treated animals, however, ceased their movements ...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/s0361-9230(79)80006-4
更新日期：1979-05-01 00:00:00
abstract：:It is now generally recognized that interleukin-6 (IL6) is one of the cytokines that mediate the various nonspecific host defense responses to infectious pathogens. Among its now well-demonstrated effects on systemic administration are fever and acute-phase proteinemia. These effects are also activated by the cytokine...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/0361-9230(90)90185-3
更新日期：1990-12-01 00:00:00
abstract：:Intracerebral hemorrhage (ICH) is a devastating subtype of stroke because it has few viable therapeutic options to intervene against primary or second brain injury. Recently, evidence has suggested that ferroptosis, a nonapoptotic form of cell death, is involved in ICH. In this study, we examined whether ICH-induced n...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/j.brainresbull.2019.08.013
更新日期：2019-11-01 00:00:00
abstract：:Cerebral ischemic damage in gerbils was assessed by locomotor activity studies and histopathological examination of the hippocampal CA1 pyramidal cell layer. Pretreatment with AICAr (50 and 500 mg/kg) 30 min prior to a 5-min ischemic episode in unanesthetized gerbils, significantly attenuated the degree of ischemic ne...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/0361-9230(90)90277-7
更新日期：1990-07-01 00:00:00
abstract：:Repeated intraventricular injection of the excitatory amino acids glutamate and aspartate for one hour produced morphologic changes in the hippocampus that were qualitatively identical to the acute and chronic changes seen in the brains of human epileptics and in experimental animals in which hippocampal seizure activ...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/0361-9230(85)90059-0
更新日期：1985-07-01 00:00:00
abstract：:An enhanced production of hypothalamic neuropeptide Y (NPY) now appears to underlie a number of hyperphagia syndromes. However, the role of NPY in the hyperphagia induced by hypothalamic lesions has not yet been explored. Here, hypothalamic lesions were induced in mice by administration of goldthioglucose (GTG) and br...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/0361-9230(92)90071-5
更新日期：1992-09-01 00:00:00
abstract：:Developing animals are more sensitive than adults to the delayed neurotoxicity caused by chlorpyrifos exposure. In developing rat brain, chlorpyrifos doses that cause no discernible systemic toxicity and only a minor degree of cholinesterase inhibition, nevertheless evoke alterations in cell function and number that a...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/s0361-9230(97)00329-8
更新日期：1998-01-01 00:00:00
abstract：:Previous work in our laboratory suggests that the indirect stimulation of prolactin gene transcription observed in male rats between 3 and 6 h following estrogen injection results from an inhibition of dopamine release from the tuberoinfundibular dopaminergic neurons. To evaluate further the role of dopamine in the re...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/0361-9230(96)00004-4
更新日期：1996-01-01 00:00:00
abstract：:Klotho, which is a life extension factor, and erythropoietin (EPO) have been introduced as effective neuroprotective factors in several neurological disorders. The present study is an attempt to examine the potential role of klotho and EPO in therapeutic effect of curcumin-loaded nanoparticles (NPs) in pentylenetetraz...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/j.brainresbull.2018.08.010
更新日期：2018-09-01 00:00:00
abstract：:Here we asked if insulin activation of the nucleus accumbens in vitro is reflected by an increase in (3)H-deoxyglucose ([(3)H]DG) uptake, thus subserving a new model to study molecular mechanisms of central insulin actions. Additionally, we investigated the dependence of this insulin effect on endocannabinoids and cor...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/j.brainresbull.2016.05.009
更新日期：2016-06-01 00:00:00
abstract：:During normal ageing, photoreceptors of the human retina undergo various structural changes. We examined retinas from 33 donors (56 eyes; age span 13-94 years) by electron microscopy to see morphological changes in the cones with ageing. We show mitochondrial alterations and occurrence of electron-dense globules in th...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/j.brainresbull.2006.09.007
更新日期：2006-12-11 00:00:00
abstract：:Cytochrome P450 2D (CYP2D) mediates the activation and inactivation of several classes of psychoactive drugs, including opioids, which can alter drug response. Tramadol is a synthetic opioid with analgesic activity of its own as well as being metabolically activated by CYP2D to O-desmethyltramadol (ODMST) an opioid re...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/j.brainresbull.2020.09.001
更新日期：2020-11-01 00:00:00
abstract：:Chronic stress, a risk factor for the development of psychiatric disorders, is known to induce alterations in neuronal networks in many brain areas. Previous studies have shown that chronic stress changes the expression of the cannabinoid receptor 1 (CB1) in the brains of adult rats, but neurophysiological consequence...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/j.brainresbull.2011.04.005
更新日期：2011-07-15 00:00:00
abstract：:Electroretinographic evoked potentials (ERGs) were recorded in dark adapted crayfish by the application of pulses of light (0.09 Cd/ft2) presented every 2.5 min. Heterolateral illumination (HI) for sixty min (0.06-0.3 Cd/ft2) induced up to 50% decrease in ERG after a latency of 12-25 min. ERG depression was proportion...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/0361-9230(78)90034-5
更新日期：1978-03-01 00:00:00
abstract：:A growing body of evidence has pointed to the NMDA receptor antagonists as a potential therapeutic target for the treatment of major depression. The present study was aimed to evaluate behavioural and molecular effects of the acute and chronic treatment with memantine and imipramine in rats. To this aim, rats were acu...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/j.brainresbull.2009.11.013
更新日期：2010-04-05 00:00:00
abstract：:Ouabain, tetrodotoxin, and calcium selective ionophore (A23187) were administered bilaterally into the hypothalamus of the unrestrained, fully conscious cat, while body temperature and other indicators of thermoregulatory responses were monitored continuously. Posterior hypothalamic microinjection of 2.0 to 10.0 ng or...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/0361-9230(80)90286-5
更新日期：1980-01-01 00:00:00
abstract：:The expression of ErbB4 mRNA was examined in dorsal thalamic regions of chicks and rats. In rats, ErbB4 expression was observed in the habenular nuclei, the paraventricular nucleus, intermediodorsal nucleus, the central medial thalamic nucleus, the posterior nucleus, the parafascicular nucleus, the subparafascicular n...
journal_title：Brain research bulletin
pub_type： 杂志文章
doi：10.1016/s0361-9230(01)00678-5
更新日期：2002-02-01 00:00:00
