No effect of anti-leprosy drugs in the prevention of Alzheimer’s disease and β-amyloid neurotoxicity

Endoh, Masumi; Kunishita, Tatsuhide; Tabira, Takeshi

doi:10.1016/s0022-510x(99)00057-x

Cited by 46 publications

(47 citation statements)

References 5 publications

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“…Clofazimine at 42.25 M (20 g/ml) induced hemolysis of murine RBCs, and the toxic effects were evident when murine macrophages were treated with 10.56 M clofazimine (23). On the other hand, clofazimine had no toxic effect on cultured neuronal cells at 211.24 M (100 g/ ml) (24). In the present study, bovine and equine RBCs were not affected, morphologically or functionally, by pretreatment with clofazimine in vitro.…”

Section: Discussioncontrasting

confidence: 51%

Clofazimine Inhibits the Growth of Babesia and Theileria Parasites In Vitro and In Vivo

Tuvshintulga

AbouLaila

Davaasuren

et al. 2016

Antimicrob Agents Chemother

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The present study evaluated the growth-inhibitory effects of clofazimine, currently used for treating leprosy, against Babesia bovis, B. bigemina, B. caballi, and Theileria equi in in vitro culture and against Babesia microti in mice. The 50% inhibitory concentrations (IC 50 s) of clofazimine against the in vitro growth of B. bovis, B. bigemina, B. caballi, and T. equi were 4.5, 3, 4.3, and 0.29 M, respectively. In mice infected with B. microti, treatment with 20 mg/kg of body weight of clofazimine administered orally resulted in a significantly lower peak parasitemia (5.3%) than that in the control group (45.9%), which was comparable to the subcutaneous administration of 25 mg/kg diminazene aceturate, the most widely used treatment for animal piroplasmosis. Although slight anemia was observed in both clofazimine-and diminazene aceturate-treated infected mice, the level and duration of anemia were lower and shorter, respectively, than those in untreated infected mice. Using blood transfusions and PCR, we also examined whether clofazimine completely killed B. microti. On day 40 postinfection, when blood analysis was performed, parasites were not found in blood smears; however, the DNA of B. microti was detected in the blood of clofaziminetreated animals and in several tissues of clofazimine-and diminazene aceturate-treated mice by PCR. The growth of parasites was observed in mice after blood transfusions from clofazimine-treated mice. In conclusion, clofazimine showed excellent inhibitory effects against Babesia and Theileria in vitro and in vivo, and further study on clofazimine is required for the future development of a novel chemotherapy with high efficacy and safety against animal piroplasmosis and, possibly, human babesiosis.

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Section: Discussioncontrasting

confidence: 51%

Clofazimine Inhibits the Growth of Babesia and Theileria Parasites In Vitro and In Vivo

Tuvshintulga

AbouLaila

Davaasuren

et al. 2016

Antimicrob Agents Chemother

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“…The literature regarding dementia in leprosy patients is limited, and the results are controversial. Compared with the general population, an epidemiology study revealed that the population of leprosy patients had a significantly low prevalence rate of senile dementia, from 2.9% to 6.25% (McGeer et al , ), but other studies have indicated that leprosy patients in leprosariums have a higher‐than‐normal rate of senile dementia, at 16.8–20.7% (Goto et al , ; Endoh et al , ). The differing results might have been due to the bias arising from the sampling of different research settings.…”

Section: Discussionmentioning

confidence: 99%

The prevalence of dementia and depression in Taiwanese institutionalized leprosy patients, and the effectiveness evaluation of reminiscence therapy—a longitudinal, single‐blind, randomized control study

Su¹,

Lin³

2011

Int J Geriat Psychiatry

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“…Ab [130] a-syn [132] IAPP [130] calcitonin [130] TTR [130] b 2 -microglubin [130] insulin [130] Ab [133] Ab plaques [133] p-tau [133] a-syn [132] unknown none conducted C2 Ab [135,146] unknown insoluble Ab [137] soluble Ab [137] unknown none conducted Baicalein Ab [138] a-syn [138,147] unknown unknown unknown none conducted iAb5p Ab [140] Ab [148] Ab plaques [148] soluble Ab [148] cognitive function [149] none conducted Rifampicin Ab [141,150] unknown soluble a-syn [151] insoluble a-syn [151] unknown none conducted www.chemmedchem.org mers and fibrils. Their results suggest that following treatment with resveratrol, both prefibrillar oligomers and fibrils form large, insoluble HMW aggregates that, consistent with the previous study, are nontoxic.…”

Section: Decrease Of Behavioral Deficitsmentioning

confidence: 99%

Modulating Self‐Assembly of Amyloidogenic Proteins as a Therapeutic Approach for Neurodegenerative Diseases: Strategies and Mechanisms

Liu

Bitan

2012

ChemMedChem

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Abnormal protein assembly causes multiple devastating disorders in the central nervous system (CNS), such as Alzheimer's, Parkinson's, Huntington's, and prion diseases. Due to the now extended human lifespan, these diseases have been increasing in prevalence, resulting in major public health problems and the associated financial difficulties worldwide. The wayward proteins that lead to disease self-associate into neurotoxic oligomers and go on to form fibrillar polymers through multiple pathways. Thus, a range of possible targets for pharmacotherapeutic intervention exists along these pathways. Many compounds have shown different levels of effectiveness in inhibiting aberrant self-assembly, dissociating existing aggregates, protecting cells against neurotoxic insults, and in some cases ameliorating disease symptoms in vivo, yet achieving efficient, disease-modifying therapy in humans remains a major unattained goal. To a large degree, this is because the mechanisms of action for these drugs are essentially unknown. For successful design of new effective drugs, it is crucial to elucidate the mechanistic details of their action, including the actual target(s) along the protein aggregation pathways, how the compounds modulate these pathways, and their effect at the cellular, tissue, organ, and organism level. Here, the current knowledge of major mechanisms by which some of the more extensively explored drug candidates work are discussed. In particular, we focus on three prominent strategies: 1) stabilizing the native fold of amyloidogenic proteins, 2) accelerating the aggregation pathways towards the fibrillar endpoint thereby reducing accumulation of toxic oligomers, and 3) modulating the assembly process towards nontoxic oligomers/aggregates. The merit of each strategy is assessed, and the key points to consider when analyzing the efficacy of possible drug candidates and their mechanism of action are discussed.

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No effect of anti-leprosy drugs in the prevention of Alzheimer’s disease and β-amyloid neurotoxicity

Cited by 46 publications

References 5 publications

Clofazimine Inhibits the Growth of Babesia and Theileria Parasites In Vitro and In Vivo

Clofazimine Inhibits the Growth of Babesia and Theileria Parasites In Vitro and In Vivo

The prevalence of dementia and depression in Taiwanese institutionalized leprosy patients, and the effectiveness evaluation of reminiscence therapy—a longitudinal, single‐blind, randomized control study

Modulating Self‐Assembly of Amyloidogenic Proteins as a Therapeutic Approach for Neurodegenerative Diseases: Strategies and Mechanisms

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