Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.1.8 (cholinesterase)
12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Moderate to severe Alzheimer's disease (AD) is characterized by increasing cognitive, functional, and behavioural dysfunction that results in increased caregiver burden and, eventually, complete dependence. Despite its significance as a societal health problem, there are few treatment trials of cognitive enhancers or disease modifying agents for this stage of illness. Studies suggest the cholinesterase inhibitors, especially donepezil, may provide benefit. Several studies provide support for the use of the NMDA receptor antagonist memantine as monotherapy or added to a cholinesterase inhibitor for moderate to severe AD. While there are no published guidelines for the treatment of moderate to severe AD, these studies do provide guidance for recommendations for study design and outcome measures. Such studies are urgently needed.
...
PMID:Treatment of moderate to severe Alzheimer's disease: rationale and trial design. 1746 92

Presenilin-1 (PS1) mutations cause many cases of early-onset inherited Alzheimer's disease, in part, by increasing the production of neurotoxic forms of amyloid beta-peptide (Abeta). However, Abeta-independent effects of mutant PS1 on neuronal Ca(2+) homeostasis and sensitivity to excitatory neurotransmitters have been reported. Here we show that cholinergic modulation of hippocampal synaptic plasticity is impaired in PS1 mutant knockin (PS1KI) mice. Whereas activation of muscarinic receptors enhances LTP at CA1 synapses of normal mice, it impairs LTP in PS1KI mice. Similarly, mutant PS1 impairs the ability of the cholinesterase inhibitor phenserine to enhance LTP. The NMDA current is decreased in CA1 neurons of PS1KI mice and is restored by intracellular Ca(2+)chelation. Similar alterations in acetylcholine and NMDA receptor-mediated components of synaptic plasticity are evident in 3xTgAD mice with PS1, amyloid precursor protein and tau mutations, suggesting that the adverse effects of mutant PS1 on synaptic plasticity can occur in the absence or presence of amyloid and tau pathologies.
...
PMID:Presenilin-1 mutation impairs cholinergic modulation of synaptic plasticity and suppresses NMDA currents in hippocampus slices. 1806 71

This chapter will focus in the currently treatments for Alzheimer Disease. The meeting points in the proposed pathogenesis of the disease are the cholinergic and the cascade amyloid hypothesis based mainly in postmortem brain changes: 1- Pathological based on greater density of neuritic plaques and the characteristic presence of neurofibrillary tangles associated with neuronal loss, synaptic alterations and evidence for chronic inflammatory reactions, 2) Biochemical based on major depletion of cortical cholinergic innervation, dramatic loss in levels of biochemically determined choline acetyltransferase, accumulation of beta-amyloid peptide, oxidation, glutamatergic excitotoxicity and activation of the apoptotic cascade. The currently available therapies based on the hypothesized pathophysiology of AD are: Acetylcholinesterase inhibitors (donepezil, rivastigmine and galantamine) and the NMDA receptor inhibitor Memantine. None of the "head to head" analyses done with cholinesterase inhibitors (CI) were able to demonstrate a between group effect for efficacy. However the treatment planning is based on their differences, their titration phase to reach the therapeutic doses, interactions and side effects. The non pharmacological treatment in the early and late stages of the disease, the different cognitive stimulation techniques and available prevention trials are also addressed and discussed.
...
PMID:[Treatment of Alzheimer's Disease cognitive symptoms]. 1839 12

Although developmental exposures of rats to low levels of the organophosphate pesticides (OPs), chlorpyrifos (CPF) or diazinon (DZN), both cause persistent neurobehavioral effects, there are important differences in their neurotoxicity. The current study extended investigation to parathion (PTN), an OP that has higher systemic toxicity than either CPF or DZN. We gave PTN on postnatal days (PND) 1-4 at doses spanning the threshold for systemic toxicity (0, 0.1 or 0.2 mg/kg/day, s.c.) and performed a battery of emotional and cognitive behavioral tests in adolescence through adulthood. The higher PTN dose increased time spent on the open arms and the number of center crossings in the plus maze, indicating greater risk-taking and overall activity. This group also showed a decrease in tactile startle response without altering prepulse inhibition, indicating a blunted acute sensorimotor reaction without alteration in sensorimotor plasticity. T-maze spontaneous alternation, novelty-suppressed feeding, preference for sweetened chocolate milk, and locomotor activity were not significantly affected by neonatal PTN exposure. During radial-arm maze acquisition, rats given the lower PTN dose committed fewer errors compared to controls and displayed lower sensitivity to the amnestic effects of the NMDA receptor blocker, dizocilpine. No PTN effects were observed with regard to the sensitivity to blockade of muscarinic and nicotinic cholinergic receptors, or serotonin 5HT(2) receptors. This study shows that neonatal PTN exposure evokes long-term changes in behavior, but the effects are less severe, and in some incidences opposite in nature, to those seen earlier for CPF or DZN, findings consistent with our neurochemical studies showing different patterns of effects and less neurotoxic damage with PTN. Our results reinforce the conclusion that low dose exposure to different OPs can have quite different neurotoxic effects, obviously unconnected to their shared property as cholinesterase inhibitors.
...
PMID:Persistent behavioral alterations in rats neonatally exposed to low doses of the organophosphate pesticide, parathion. 1881 54

Alzheimer's disease is an ever-increasing health concern among the aging population, and as we research new and existing treatments for this disease we begin to uncover possibilities for its prevention. Observational studies and animal models have provided promising findings and generated excitement, but placebo-controlled clinical trials are required to demonstrate true efficacy for these treatments.In the past two decades, clinical trials have led to the approval of symptomatic treatments for Alzheimer's disease, including cholinesterase inhibitors and, more recently, an NMDA receptor antagonist. Clinical trials have also examined antioxidants, NSAIDs, hormone replacement, nutritional supplements and nonpharmacological interventions for the treatment and prevention of Alzheimer's disease. While the results of many of these trials have been disappointing, new mechanisms targeting the hallmark pathology of Alzheimer's disease are currently under investigation, including immunotherapy and secretase modulation, targeted at reducing the amyloid burden, for which we await the results. We review the evidence from completed trials, support for ongoing studies and propose directions for future research.
...
PMID:Preventing Alzheimer's disease : separating fact from fiction. 1884 31

The percentage of Taiwanese aged 65 years and older has been increasing over the past 27 years, from 4.1% in 1980 to 10.2% in 2007. Studies on the Taiwan population have shown that the prevalence of dementia is approximately 1.7 - 4.3% among aged people, and that the most common cause of dementia is Alzheimer's disease (AD). However, compared to Western countries, this is a low prevalence rate, which might be due to the simple lifestyle led by aged Taiwanese, a selective higher mortality rate in Taiwanese, and a low prevalence of the APOE4 allele in Taiwanese. The current evaluation of dementia in Taiwan derives from several reliable and valid cognitive and behavioral assessment tools originally developed in Western countries. These tools are not only useful for clinical evaluation, but also have offered a method for possible cross-cultural assessment. Behavioral and psychiatric symptoms of dementia in Taiwan have been shown to be similar to other ethnic groups, except for a relative high prevalence of apathy. Although three cholinesterase inhibitors and one glutamate NMDA receptor antagonist are available in Taiwan to treat dementia, their insurance reimbursement is strictly regulated and only a small proportion of patients with AD receive medical treatment. A local consensus of and guideline for diagnosis and treatment of dementia is needed in Taiwan.
...
PMID:Dementia in Taiwan: past, present, and future. 1897 20

Alzheimer's disease (AD) is the most common cause of dementia, accounting for 25 million cases worldwide. Until recently, the pharmacotherapy of AD was limited to the use of cholinesterase inhibitors (ChEIs) that are approved only for the mild to moderate stages of the illness. Memantine, an NMDA receptor antagonist has been found to be effective, both as monotherapy and in combination with donepezil, in the treatment of patients with moderate to severe stage AD. More recent studies have examined the role of memantine in the treatment of the mild to moderate stages of the disease, although the collective results of these studies remain inconclusive. Available pharmacoeconomic data indicate that treatment with memantine is cost-effective when compared with no treatment in patients with moderate to severe AD. Memantine treatment is predicted to be associated with lower costs of care, longer time to dependence and institutionalization, and gains in quality-adjusted life-years. In this article, we review the evidence for the use of memantine in patients with AD, ranging from the mild to severe stages of disease.
...
PMID:Memantine: efficacy and safety in mild-to-severe Alzheimer's disease. 1930 May 57

The mainstay of current management of patients with Alzheimer's disease involves drugs that provide symptomatic therapy. Research approaches for future therapy of Alzheimer's disease are focusing on disease modifying and/or preventive approaches. Two classes of medications have been approved by the US FDA for the treatment of Alzheimer's disease: the cholinesterase inhibitors (tacrine, donepezil, rivastigmine, galantamine), mostly for mild to moderate Alzheimer's disease, and the noncompetitive NMDA receptor antagonist memantine for the moderate to severe stages of Alzheimer's disease. Management of comorbid medical problems can be more complex in patients with dementia than in those without dementia. Unfortunately, medication adherence in Alzheimer's disease is low and good adherence is essential for attempting to slow disease progression and improve or stabilize quality of life. Simplifying treatment regimens and providing more caregiver- and patient-friendly modes of administration that fit in better with daily routines can ease caregiver stress which, in turn, may have a favourable impact on the patient's condition. To overcome problems of medication adherence in the elderly, simple, user-friendly dosage regimens should be prescribed for all medications; thus the need for novel regimens and delivery systems in the pharmacological treatment of Alzheimer's disease, such as once-daily donepezil, memantine and galantamine, and transdermal rivastigmine.
...
PMID:Novel regimens and delivery systems in the pharmacological treatment of Alzheimer's disease. 1937 59

Object location task (OLT) has been used as a model of hippocampal-dependent memory. Despite this application, there is neither a consistent pharmacological validation of NMDA receptor modulation nor an evaluation of hippocampal participation in mice. In the OLT, mice were placed in the open field with two identical objects for 3 min and, after a delay of 30, 90, 180 or 360 min, one object was moved to a new location and the time spent exploring the objects in new, (novel) and old (familiar) locations was recorded. Our results showed that the mice were able to discriminate object location when tested either 90 or 180 min after training. Intraperitoneal administration of MK801 (NMDA receptors antagonist) or scopolamine (mACh antagonist) induced amnesic effects. On the other hand, D-cycloserine (NMDA agonist) or tacrine (cholinesterase inhibitor) were able to improve memory in the mice tested. In addition, lidocaine infusion in the hippocampal CA1 region 10 min before training blocked object location memory. In short, this work indicates that OLT is susceptible to modulation of NMDA receptors, cholinergic neurotransmission and it is the first to characterize the participation of the hippocampal CA1 region, in this task.
...
PMID:Object location memory in mice: pharmacological validation and further evidence of hippocampal CA1 participation. 1952 94

Alzheimer's disease (AD) is an age-related neurodegenerative disease increasingly recognized as one of the most important medical problems affecting the elderly. Although a number of drugs, including several cholinesterase inhibitors and an NMDA receptor antagonist, have been approved for use, they have been shown to produce diverse side effects and yield relatively modest benefits. To overcome these limitations of current therapeutics for AD, extensive research and development are underway to identify drugs that are effective and free of undesirable side effects. Certain naturally occurring dietary polyphenolic phytochemicals have received considerable recent attention as alternative candidates for AD therapy. In particular, curcumin, resveratrol, and green tea catechins have been suggested to have the potential to prevent AD because of their anti-amyloidogenic, anti-oxidative, and anti-inflammatory properties. These polyphenolic phytochemicals also activate adaptive cellular stress responses, called 'neurohormesis', and suppress disease processes. In this commentary, we describe the amyloid-beta-induced pathogenesis of AD, and summarize the intracellular and molecular targets of selected dietary phytochemicals that might slow the progression of AD.
...
PMID:Naturally occurring phytochemicals for the prevention of Alzheimer's disease. 2005 Sep 72


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

---