Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human hypothalamus is involved in a wide range of functions in the developing, adult and aging subject and is responsible for a large number of symptoms of neuroendocrine, neurological and psychiatric diseases. In the present review some prominent hypothalamic nuclei are discussed in relation to normal development, sexual differentiation, aging and a number of neuropathological conditions. The suprachiasmatic nucleus, the clock of the brain, shows seasonal and circadian variations in its vasopressin neurons. During normal aging, but even more so in Alzheimer's disease, the number of these neurons decreases. In homosexual men this nucleus is larger than in heterosexual men. The difference between the sexually dimorphic nuclei of men and women arises between the ages of 2-4 to puberty. In adult men this nucleus is twice as large as in adult women. In the process of aging, a sex-dependent decrease in cell number occurs. The vasopressin and oxytocin cells of the supraoptic and paraventricular nucleus are present in adult numbers as early as mid-gestation. Lower oxytocin neuron numbers are found in Prader-Willi syndrome, AIDS and Parkinson's disease. Familial hypothalamic diabetes insipidus is based upon a point mutation in the vasopressin-neurophysin-glycopeptide gene. Parvicellular corticotropin-releasing hormone-containing neurons in the paraventricular nucleus increase in number and are activated during the course of aging. In post-menopausal women, the infundibular or arcuate nucleus contains hypertrophic neurons containing oestrogen receptors. These neurons may be involved in the initiation of menopausal flushes. The nucleus tuberalis lateralis may be involved in feeding behaviour and metabolism. In Huntington's disease the majority of its neurons is lost; in Alzheimer's disease it shows very strong cytoskeletal alterations. Tuberomammillary nucleus neurons contain, e.g., histamine or galanine, and project to the cortex. Strong cytoskeletal changes, as well as plaques and tangles are found in this nucleus in Alzheimer's disease. The various hypothalamic nuclei are probably involved in many functions and symptoms of which only a minority has been revealed.
 ...
PMID:Functional neuroanatomy and neuropathology of the human hypothalamus. 851 84

Acetyl-L-carnitine (ALCAR) is a drug currently under investigation for Alzheimer disease (AD) therapy. ALCAR seems to exert a number of central nervous system (CNS)-related effects, even though a clear pharmacological action that could explain clinical results in AD has not been identified yet. The aim of this study was to determine cerebrospinal fluid (CSF) and plasma biological correlates of ALCAR effects in AD after a short-term, high-dose, intravenous, open treatment. Results show that ALCAR CSF levels achieved under treatment were significantly higher than the ones at baseline, reflecting a good penetration through the blood-brain barrier and thus a direct CNS challenge. ALCAR treatment produced no apparent change on CSF classic neurotransmitters and their metabolite levels (homovanillic acid, 5-hydroxyindoleacetic acid, MHPG, dopamine, choline). Among CSF peptides, while corticotropin-releasing hormone and adrenocorticotropic hormone remained unchanged, beta-endorphins significantly decreased after treatment; plasma cortisol levels matched this reduction. Since both CSF beta-endorphins and plasma cortisol decreased, one possible explanation is that ALCAR reduced the AD-dependent hypothalamic-pituitary-adrenocortical (HPA) axis hyperactivity. At present, no clear explanation can be proposed for the specific mechanism of this action.
Alzheimer Dis Assoc Disord 1995
PMID:Acetyl-L-carnitine in Alzheimer disease: a short-term study on CSF neurotransmitters and neuropeptides. 853 10

Cerebrospinal fluid (CSF) levels of several neuropeptides have been suggested as candidate markers in neurodegenerative disorders. We have examined the levels of corticotropin-releasing hormone (CRH), beta-endorphine (BEND), delta sleep-inducing peptide (DSIP), somatostatin (SRIF), and neuropeptide Y (NPY) in CSF samples obtained under highly standardized conditions from healthy aged controls and from patients suffering from Alzheimer's disease (AD) or vascular dementia (VAD). The influence of some potentially confounding factors was evaluated. CRH and BEND were markedly decreased in both AD and VAD patients, and BEND levels correlated negatively with degree of dementia within the patient population. SRIF was decreased in both AD and VAD patients. DSIP was slightly increased in AD, but not in VAD. NPY did not differ between groups. For none of the peptides did CSF concentrations correlate significantly with duration of illness, nor, with the exception of BEND, with its degree. Present data do not support the hypothesis that specific neuropeptide changes occur in different neurodegenerative disorders, but are in agreement with previous reports suggesting that neuropeptide systems are differentially affected by neurodegeneration.
 ...
PMID:Cerebrospinal fluid neuropeptides in Alzheimer's disease and vascular dementia. 854 42

We have reported that arecoline, a muscarinic receptor agonist replicably enhanced verbal memory in five of nine subjects with Alzheimer's disease (AD). To investigate the mechanism of cognitive improvement, circulating hormone measurements were made during high-dose acute and low-dose chronic intravenous (i.v.) arecoline administration to AD patients. Acute hormone responses were measured during, and for 6 h after, infusion of arecoline 5 mg i.v. over 30 min. Chronic responses were measured in cognitive responders during continuous i.v. infusion of arecoline escalating over 2 weeks (0.5-40 mg/day) and then during a 1 week infusion of the dose optimizing cognition (4-16 mg/day). Acute arecoline administered to 14 subjects produced unpleasant side-effects (e.g. nausea, vomiting), mean adrenocorticotrophic hormone (p = .0006), cortisol (p = .0001) and beta-endorphin (p = .0001) levels were elevated. During chronic arecoline treatment, no side-effects occurred and plasma cortisol, adrenocorticotrophic hormone and beta-endorphin levels were unchanged in nine subjects overall and in five cognitive responders. Thus, high-dose arecoline activates the hypothalamic-pituitary-adrenal (HPA) axis and may increase other anterior pituitary hormone levels, likely representing a 'stress response', but cognition-enhancing, low doses of arecoline do not produce a glucocorticoid response. Hence, arecoline-induced memory improvement is not due to the induction of 'stress' nor to the elevation of peripheral corticosteroid levels.
 ...
PMID:Neuroendocrine responses to intravenous infusion of arecoline in patients with Alzheimer's disease. 858 3

Previous studies suggest disturbances in the central regulation of the hypothalamic-pituitary-adrenocortical axis (HPA) in advanced Alzheimer's disease (AD). In this study the reactivity of the HPA axis was evaluated by stimulation with corticotropin-releasing hormone (CRH) of patients with mild to moderate AD. Twenty-three patients with AD (aged 61-88 yr) and 19 healthy elderly (aged 62-84 yr) received an intravenous bolus injection of human CRH (1 microgram/kg) at 3:00 PM. CRH-stimulated plasma ACTH levels were significantly lower in AD patients, while serum cortisol, dehydroepiandrosterone, and androstenedione responses relative to the amount of ACTH released were higher in AD patients. Significant correlations were found between low basal plasma ACTH levels and temporal lobe atrophy (p=0.02) and between peak plasma ACTH levels and hippocampal atrophy (p = 0.01). These findings suggest abnormalities at several levels of HPA axis in AD.
 ...
PMID:Blunted adrenocorticotropin and increased adrenal steroid response to human corticotropin-releasing hormone in Alzheimer's disease. 975 63

Neuropeptide concentrations were determined in the postmortem cerebral cortex from 19 cognitive-impaired schizophrenics, 4 normal elderly subjects, 4 multi-infarct dementia (MID) cases, and 13 Alzheimer's disease (AD) patients. Only AD patients met criteria for AD. The normal elderly and MID cases were combined into one control group. Somatostatin concentrations were reduced in both schizophrenia and AD. Neuropeptide Y concentrations were reduced only in schizophrenia, and corticotropin-releasing hormone concentrations were primarily reduced in AD. Concentrations of vasoactive intestinal polypeptide and cholecystokinin also were reduced in schizophrenia, although not as profoundly as somatostatin or neuropeptide Y. In AD, cholecystokinin and vasoactive intestinal peptide were unchanged. Neuropeptide deficits in schizophrenics were more pronounced in the temporal and frontal lobes than in the occipital lobe. The mechanisms underlying these deficits in schizophrenia and AD are likely distinct. In schizophrenia, a common neural element, perhaps the cerebral cortical gaba-aminobutyric acid (GABA)-containing neuron, may underlie these deficits.
 ...
PMID:Neuropeptide deficits in schizophrenia vs. Alzheimer's disease cerebral cortex. 871 4

We asked whether hypothalamic-pituitary-adrenocortical (HPA) axis responses to a cholinergic stimulus are blunted in patients with Alzheimer's disease (AD) of mild to moderate severity. Such a finding would be consistent with a central cholinergic deficiency early in the course of AD. To address this question, we measured the plasma adrenocorticotropic hormone (ACTH), beta-endorphin-like immunoreactivity (beta E-LI), and cortisol responses to the cholinesterase inhibitor physostigmine in 10 healthy normal older subjects (age = 71 +/- 2 years) and 11 outpatients with probable AD (age = 72 +/- 2 years; Mini Mental State Exam score = 19 +/- 2). Cortisol concentrations were higher in AD subjects throughout the study, but AD and normal older subjects had similar robust ACTH, beta E-LI, and cortisol responses to physostigmine. In all subjects combined, women had greater ACTH, beta E-LI, and cortisol responses to physostigmine than did men. Plasma physostigmine concentrations did not differ between groups. These results suggest that female gender enhances the magnitude of HPA axis responses to cholinergic stimulation in older humans; however, the HPA axis response to physostigmine does not appear to reflect central cholinergic deficiency in the early stages of AD.
 ...
PMID:Hypothalamic-pituitary-adrenocortical axis responses to physostigmine: effects of Alzheimer's disease and gender. 878 Aug 56

In the Alzheimer disease (AD) brain, senile plaques contain several proteins and cytokines, such as beta-amyloid protein (A beta), interleukin 1, transforming growth factor beta 1 (TGF beta 1), and apolipoprotein E, which may contribute to the process of neurodegeneration. Clusterin is also known to colocalize with A beta deposits in neuritic plaques. Clusterin is a multifunctional protein that causes cell aggregation, binds to beta-endorphin, and inhibits the terminal complex formation of complement. Clusterin mRNA and protein are increased in the brains of AD patients. Cytokines such as TGF beta 1 and interleukin 1 enhance the expression of clusterin, which may link clusterin to inflammatory mechanisms in AD. A beta, a 39-43 amino acid peptide, is a major component of the senile plaques that are characteristic of AD. Highly aggregated A beta is implicated in neurodegeneration, e.g., A beta aggregates spontaneously into fibrillar forms resembling those in plaques that, in experimental models, cause neurotoxicity through oxidative stress. Clusterin inhibits the aggregation of A beta, which might be neuroprotective according to the aggregation-toxicity hypothesis of A beta. However, clusterin enhanced the oxidative stress of A beta. This may extend its neurotoxicity to locations distal from plaques wherever A beta is present.
 ...
PMID:Relationship between multifunctional protein "clusterin" and Alzheimer disease. 889 44

Although neuritic and diffuse plaques generally coexist in Alzheimer disease (AD) neocortex, the predominance of diffuse plaques in the striatum prompted us to explore the potential influence of striatal features such as the striatal mosaic on beta-amyloid (A beta) deposition. Using double immunohistochemistry with an antibody to A beta in combination with antibodies to met-enkephalin or somatostatin, we investigated the relationship between diffuse plaques and neuropeptide distribution in the dorsal striatum. This relationship was examined in "pure" AD cases as well as in AD cases with coexisting Parkinson disease (PD) pathology, i.e. nigral degeneration and Lewy bodies at any site (AD + PD). Despite the presence of numerous A beta-positive diffuse plaques in both groups, the mosaic pattern, as exemplified by met-enkephalin-immunoreactive patches, was preserved. No obvious association was observed between the plaques and met-enkephalin-positive patches or somatostatin-immunoreactive neurons. Tyrosine hydroxylase immunoreactivity in the matrix was, however, diminished in AD + PD, most likely reflecting the nigral degeneration in these cases. Overall, these observations suggest that neostriatal A beta deposition in AD is not influenced by environmental factors associated with the striatal mosaic.
 ...
PMID:Diffuse plaques in the striatum in Alzheimer disease (AD): relationship to the striatal mosaic and selected neuropeptide markers. 941 85

The association between Alzheimer caregiving and natural killer (NK) cell activity and basal plasma levels of adrenocorticotropic hormone (ACTH), cortisol, beta-endorphin, prolactin, epinephrine, norepinephrine, and neuropeptide Y was determined in 100 spousal Alzheimer caregivers and 33 age- and gender-comparable control volunteers upon intake into a study of the psychological and physiologic impact of caregiving. The relationship between these physiologic measures and individual characteristics such as age, gender, medical status, severity of stress, severity of depressive symptoms, and caregiver burden was tested. In addition, the association between NK activity and alterations of the neuroendocrine measures was investigated. As compared to controls, the Alzheimer caregivers had similar levels of NK activity and of basal plasma neuroendocrine hormones and sympathetic measures. While older age and male gender status were associated with increased levels of ACTH, neither medical caseness, severity of life stress, nor severity of depressive symptoms was associated with alterations in any of the multiple physiologic domains. Classification of Alzheimer caregiver burden identified caregivers who were mismatched in terms of the amount of care they were required to provide and the amount of respite time received. The mismatched caregivers had significantly higher basal plasma ACTH but no change in other physiological measures, as compared to non-mismatched caregivers. NK activity was negatively correlated with plasma levels of neuropeptide Y but not with any of the other neuroendocrine measures. Based on this cross-sectional evaluation of NK activity and neuroendocrine and sympathetic measures, we conclude that most Alzheimer caregivers do not show evidence of altered basal physiology.
 ...
PMID:Alzheimer caregiver stress: basal natural killer cell activity, pituitary-adrenal cortical function, and sympathetic tone. 960 82


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>