Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Huperzine A (HupA), isolated from Chinese herb Huperzia serrata, is a potent, highly specific and reversible inhibitor of acetylcholinesterase. It has been found to reverse or attenuate cognitive deficits in a broad range of animal models. Clinical trials in China have demonstrated that HupA significantly relieves memory deficits in aged subjects, patients with benign senescent forgetfulness, Alzheimer's disease (AD) and vascular dementia (VD), with minimal peripheral cholinergic side effects compared with other AChEIs in use. HupA possesses the ability to protect cells against hydrogen peroxide, beta-amyloid protein (or peptide), glutamate, ischemia and staurosporine-induced cytotoxicity and apoptosis. These protective effects are related to its ability to attenuate oxidative stress, regulate the expression of apoptotic proteins Bcl-2, Bax, P53 and caspase-3, protect mitochondria, and interfere with APP metabolism. Antagonizing effects on NMDA receptors and potassium currents may contribute to the neuroprotection as well. It is also possible that the non-catalytic function of AChE is involved in neuroprotective effects of HupA. The therapeutic effects of HupA on AD or VD are probably exerted via a multi-target mechanism.
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PMID:Neuroprotective effects of huperzine A. A natural cholinesterase inhibitor for the treatment of Alzheimer's disease. 1595 16

Huperzine A (HupA), a novel alkaloid isolated from the Chinese herb Huperzia serrata, is a potent, highly specific and reversible inhibitor of acetylcholinesterase(AChE). Compared with tacrine, donepezil, and rivastigmine, HupA has better penetration through the blood-brain barrier, higher oral bioavailability, and longer duration of AChE inhibitory action. HupA has been found to improve cognitive deficits in a broad range of animal models. HupA possesses the ability to protect cells against hydrogen peroxide, beta-amyloid protein (or peptide), glutamate, ischemia and staurosporine-induced cytotoxicity and apoptosis. These protective effects are related to its ability to attenuate oxidative stress, regulate the expression of apoptotic proteins Bcl-2, Bax, P53, and caspase-3, protect mitochondria, upregulate nerve growth factor and its receptors, and interfere with amyloid precursor protein metabolism. Antagonizing effects of HupA on N-methyl-D-aspartate receptors and potassium currents may also contribute to its neuroprotection as well. Pharmacokinetic studies in rodents, canines, and healthy human volunteers indicated that HupA was absorbed rapidly, distributed widely in the body, and eliminated at a moderate rate with the property of slow and prolonged release after oral administration. Animal and clinical safety tests showed that HupA had no unexpected toxicity, particularly the dose-limiting hepatotoxicity induced by tacrine. The phase IV clinical trials in China have demonstrated that HupA significantly improved memory deficits in elderly people with benign senescent forgetfulness, and patients with Alzheimer disease and vascular dementia, with minimal peripheral cholinergic side effects and no unexpected toxicity. HupA can also be used as a protective agent against organophosphate intoxication.
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PMID:Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine. 1636 7

Glioneuronal tumor with neuropil-like islands (GTNI) is a distinctive and rare tumor characterized by both glial and neuronal differentiation. However, unlike other mixed glioneuronal tumors, which are characterized by a favorable prognosis, this neoplasm has been found to be potentially aggressive. We report here a case arising in a 60-year old male patient who presented with seizures, forgetfulness and right-sided hemiparesis, due to a left frontal lobe tumor. Unlike most cases described in the literature, the present tumor was unique in its radiological appearance, which was cystic. On microscopic evaluation, the glial component was chiefly gemistocytic punctuated by neuropil-like islands. Strong nuclear immunolabeling of p53 and absence of 1p/19q deletion by fluorescence in situ hybridization assay were consistent with those in previous reports.
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PMID:Glioneuronal tumor with neuropil-like islands: a new entity. 1856 2