Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0751295 (memory loss)
 3,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alzheimer's disease is a degenerative disorder of the human central nervous system that results in a progressive loss of memory and intellectual abilities. It is strongly related to aging and it is thus assumed that 0.5% of the total population, and up to 30% of eighty-year-olds suffer from the disease. Many require expensive institutional care, often over long periods, as there is no effective treatment at present. Abundant amyloid plaques and neurofibrillary tangles constitute the two major neuropathological lesions that characterize the brains of patients with Alzheimer's disease. The amyloid plaque consists mainly of a soluble polypeptide of 42-43 amino acids called beta-amyloid. beta-Amyloids is derived by an alternative cleavage of the much larger amyloid precursor protein (APP), but it is not known which proteolytic enzyme is responsible for this alternative cleavage. In contrast to plaques, the neurofibrillary tangles are formed intracellularly and the number of them seems to correlate with the progression of the disease. Their main components are paired helical filaments (PHF) which seem to consist almost entirely of the protein tau. The normal function of tau is to bind to microtubules and thereby stabilize the nerve cell's structure and integrity. In contrast to normal tau, PHF-tau is heavily phosphorylated, and it is assumed that this phosphorylation is the underlying cause of the formation of PHF and the neurofibrillary tangles. Despite extensive research it is still not known which enzymes are responsible for the over phosphorylation of tau that occurs in Alzheimer's disease. If they could be identified and controlled pharmacologically, an effective treatment of the disease might be possible.
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PMID:[Tau, amyloid and Alzheimer's disease]. 811 89

Alzheimer's disease (AD) is a neurodegenerative condition, believed to be irreversible, characterized by inexorable deterioration of memory and intellect, with neuronal loss accompanying amyloid plaques and neurofibrillary tangles. In an amyloid precursor protein transgenic mouse model, Tg2576, little or no neuronal loss accompanies age-related memory impairment or the accumulation of Abeta, a 40-42 aa polypeptide found in plaques. Recently, we have shown inverse correlations between brain Abeta and memory in Tg2576 mice stratified by age (Westerman et al., 2002). Broadening the age range examined obscured this relationship, leading us to propose that small, soluble assemblies of Abeta disrupt cognitive function in these mice. Here we show that memory loss can be fully reversed in Tg2576 mice using intraperitoneally administered BAM-10, a monoclonal antibody recognizing the N terminus of Abeta. The beneficial effect of BAM-10 was not associated with a significant Abeta reduction, but instead eliminated the inverse relationship between brain Abeta and memory. We postulate that BAM-10 acts by neutralizing Abeta assemblies in the brain that impair cognitive function. Our results indicate that a substantial portion of memory loss in Tg2576 mice is not permanent. If these Abeta assemblies contribute significantly to memory loss in AD, then successfully targeting them might improve memory in some AD patients.
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PMID:Reversible memory loss in a mouse transgenic model of Alzheimer's disease. 1215 10

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, accompanied by memory loss and cognitive impairments, and there is no effective treatment for it at present. Since type 2 diabetes (T2DM) has been identified as a risk factor for AD, the incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP), promising antidiabetic agents for the treatment of type 2 diabetes, have been tested in models of neurodegenerative disease including AD and achieved good results. Here we show for the first time the potential neuroprotective effect of a novel dual GLP-1/GIP receptor agonist (DA-JC4) in the icv. streptozotocin (STZ)-induced AD rat model. Treatment with DA-JC4 (10nmol/kg ip.) once-daily for 14days after STZ intracerebroventricular (ICV) administration significantly prevented spatial learning deficits in a Y- maze test and Morris water maze tests, and decreased phosphorylated tau levels in the rat cerebral cortex and hippocampus. DA-JC4 also alleviated the chronic inflammation response in the brain (GFAP-positive astrocytes, IBA1-positive microglia). Apoptosis was reduced as shown in the reduced ratio of pro-apoptotic BAX to anti- apoptotic Bcl-2 levels. Importantly, insulin signaling was re-sensitized as evidenced by a reduction of phospho-IRS1Ser1101 levels and phospho-AktSer473 up-regulation. In conclusion, the novel dual agonist DA-JC4 shows promise as a novel treatment for sporadic AD, and reactivating insulin signaling pathways may be a key mechanism that prevents disease progression in AD.
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PMID:A novel dual GLP-1/GIP receptor agonist alleviates cognitive decline by re-sensitizing insulin signaling in the Alzheimer icv. STZ rat model. 2834 71