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AD Therapy (ad + therapy)
Selected AbstractsDisease modifying therapy for AD?,JOURNAL OF NEUROCHEMISTRY, Issue 3 2006Todd E. Golde Alzheimer's disease (AD) is the most common form of dementia in industrialized nations. If more effective therapies are not developed that either prevent AD or block progression of the disease in its very early stages, the economic and societal cost of caring for AD patients will be devastating. Only two types of drugs are currently approved for the treatment of AD: inhibitors of acetyl cholinesterase, which symptomatically enhance cognitive state to some degree but are not disease modifying; and the adamantane derivative, memantine. Memantine preferentially blocks excessive NMDA receptor activity without disrupting normal receptor activity and is thought to be a neuroprotective agent that blocks excitotoxicty. Memantine therefore may have a potentially disease modifying effect in multiple neurodegenerative conditions. An improved understanding of the pathogeneses of AD has now led to the identification of numerous therapeutic targets designed to alter amyloid , protein (A,) or tau accumulation. Therapies that alter A, and tau through these various targets are likely to have significant disease modifying effects. Many of these targets have been validated in proof of concept studies in preclinical animal models, and some potentially disease modifying therapies targeting A, or tau are being tested in the clinic. This review will highlight both the promise of and the obstacles to developing such disease modifying AD therapies. [source] REVIEW: Curcumin and Alzheimer's DiseaseCNS: NEUROSCIENCE AND THERAPEUTICS, Issue 5 2010Tsuyoshi Hamaguchi Curcumin has a long history of use as a traditional remedy and food in Asia. Many studies have reported that curcumin has various beneficial properties, such as antioxidant, antiinflammatory, and antitumor. Because of the reported effects of curcumin on tumors, many clinical trials have been performed to elucidate curcumin's effects on cancers. Recent reports have suggested therapeutic potential of curcumin in the pathophysiology of Alzheimer's disease (AD). In in vitro studies, curcumin has been reported to inhibit amyloid-,-protein (A,) aggregation, and A,-induced inflammation, as well as the activities of ,-secretase and acetylcholinesterase. In in vivo studies, oral administration of curcumin has resulted in the inhibition of A, deposition, A, oligomerization, and tau phosphorylation in the brains of AD animal models, and improvements in behavioral impairment in animal models. These findings suggest that curcumin might be one of the most promising compounds for the development of AD therapies. At present, four clinical trials concerning the effects of curcumin on AD has been conducted. Two of them that were performed in China and USA have been reported no significant differences in changes in cognitive function between placebo and curcumin groups, and no results have been reported from two other clinical studies. Additional trials are necessary to determine the clinical usefulness of curcumin in the prevention and treatment of AD. [source] Nonsteroidal antiinflammatory drugs as therapeutic agents for Alzheimer's diseaseDRUG DEVELOPMENT RESEARCH, Issue 3 2002Todd E. Golde One feature of the end-stage pathology of Alzheimer's disease (AD) is the presence of numerous inflammatory markers associated with the amyloid , protein (A,) deposits in the brain. Experimental data strongly suggests that A, aggregates can incite an inflammatory response, but there are also data suggesting that inflammation can promote A, production and deposition. Thus, antiinflammatory drugs may have some role in AD therapy. This idea is supported by epidemiologic data, which shows that long-term use of nonsteroidal antiinflammatory drugs (NSAIDs) confers protection from the development of AD. Significantly, oral salicylates have not been consistently shown to confer protection. Such studies have raised questions regarding the target or targets of NSAIDs that account for their apparent protection from AD. We have recently found that some NSAIDs have a novel mechanism of action, namely, selective lowering of the pathogenic A,42 peptide, that could contribute to their efficacy in AD. Further study will be needed to determine if the classic antiinflammatory properties of NSAIDs, the A,42-lowering property, another known or unknown property, or a combination of these contributes to NSAIDs apparent ability to protect individuals from the development of AD. Drug Dev. Res. 56:415,420, 2002. © Wiley-Liss, Inc. [source] Targeting Alzheimer's disease: Is there a light at the end of the tunnel?DRUG DEVELOPMENT RESEARCH, Issue 2 2002David Gurwitz Abstract The prevalence of Alzheimer's disease (AD) is on the rise in developed nations as a consequence of longer human lifespan. Current costs to society are alarming, and are projected to become even more demanding on future health budgets. Considering the relative success of Parkinson's disease pharmacotherapy, the success of AD therapy has been disappointing. Quite a few novel and promising AD drug targets are presented in this special issue of Drug Development Research. These are built on countless research studies, by many bright minds, carried out over the last several decades. However, the answer to the growing AD threat must include reliable and accurate tools, presently lacking, for its early diagnosis in at-risk individuals. Drug Dev. Res. 56:45,48, 2002. © 2002 Wiley-Liss, Inc. [source] Antisense MDM2 oligonucleotides restore the apoptotic response of prostate cancer cells to androgen deprivation,THE PROSTATE, Issue 3 2004Zhaomei Mu Abstract BACKGROUND Early in the malignant transformation of prostate epithelial cells, the apoptotic response to androgen deprivation (AD) is lost and the principle response is a slowing of cell growth. In this study, we tested whether interruption of MDM2 function using antisense MDM2 oligonucleotide (AS) affects the apoptotic response of prostate cancer cells to AD. METHODS Wild type LNCaP cells and MDM2-overexpressing (LNCaP-MST) cells were treated with AS alone or in combination with AD. Protein levels of MDM2, p53, and p21 were determined by Western blotting. Cell viability was measure by trypan blue staining. Apoptotic cell death was confirmed by cell morphological changes, annexin V/propidium iodide staining and caspase-3,+,7 activity. Overall cell survival was quantified by clonogenic assay. RESULTS AS inhibited MDM2 expression to a greater extent in LNCaP cells, as compared to LNCaP-MST cells. AS enhanced the expression of p53 and p21 in both cell lines. The growth inhibitory and cell death effects of AS,+,AD were generally greater than AS alone in LNCaP cells. Treatment of LNCaP cells with AS,+,AD for 72 hr caused a significant increase in cell death (66%) over AD alone (13%), AS alone (33%), or AD,+,AS,+,R1881 (34% with synthetic androgen replacement) that was attributable mainly to apoptosis. Clonogenic survival reflected the same pattern. CONCLUSIONS Our results suggest that the apoptotic response of prostate cancer to AD is strongly influenced by MDM2 expression. Antisense MDM2 has broad potential as a therapeutic agent to sensitize prostate cancer cells to AD therapy by enhancing apoptotic cell death. © 2004 Wiley-Liss, Inc. [source] Ibuprofen and Lipoic Acid Diamides as Potential Codrugs with Neuroprotective ActivityARCHIV DER PHARMAZIE, Issue 3 2010Piera Sozio Abstract Current evidences support the hypothesis that non-steroidal anti-inflammatory drugs (NSAIDs) and antioxidant therapy might protect against the development of Alzheimer's disease (AD). In the present work, our attention was focused on ibuprofen (IBU) used in clinical trails to prevent Alzheimer's disease, and (R)-,-lipoic acid (LA) considered as a potential neuroprotective agent in AD therapy. In particular, we investigated a series of lipophilic molecular combinations obtained by joining (R)-,-lipoic acid and ibuprofen via an amide bond. These new entities might allow targeted delivery of the parent drugs to neurons, where cellular oxidative stress and inflammation seem related to Alzheimer's disease. Our study included the synthesis of conjugates 1,3 and the evaluation of their physicochemical and in-vitro antioxidant properties. The new compounds are extremely stable in aqueous buffer solutions (pH = 1.3 and 7.4), and in rat and human plasma they showed a slow bioconversion to ibuprofen and (R)-,-lipoic acid. Codrugs 1,3 displayed in vitro free radical scavenging activity and were hydrolyzed more rapidly in brain tissue than in rat serum indicating that these new entities might allow targeted delivery of the parent drugs to neurons. The immunohistochemical analysis of A, (1-40) protein showed that A,-injected cerebral cortices treated with ibuprofen or compound 1 showed few plaques within capillary vessels and, in particular, A, (1-40) protein was less expressed in codrug- 1 -treated than in ibuprofen-treated cerebral cortex. [source] | |||||||||||||