NeuroAiD® (MLC601) and Amyloid Precursor Protein Processing

Lim, Yun-An; Murray, Lynne A.; Lai, Mitchell K.P.; Chen, C

doi:10.1159/000346236

Cited by 13 publications

(16 citation statements)

References 98 publications

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“…Similar with our result of icariin, cerebrolysin treatment significantly reduced the levels of Full-length APP in APP Tg mice 27. NeuroAiD®, also known as MLC601, obviously decreased full-length APP levels in APP transfected SH-SY5Y cells 28. In these reports, the authors did not explain the underlying mechanism of altered APP levels.…”

Section: Discussionsupporting

confidence: 77%

Icariin Decreases the Expression of APP and BACE-1 and Reduces the β-amyloid Burden in an APP Transgenic Mouse Model of Alzheimer's Disease

Zhang¹,

Shen²,

Chu³

et al. 2014

Int. J. Biol. Sci.

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Objective: The purpose of this study was to investigate the effects and pharmacological mechanisms of icariin, which is the main component in the traditional Chinese herb Epimedium, on β-amyloid (Aβ) production in an amyloid precursor protein (APP) transgenic (Tg) mouse model of Alzheimer's disease (AD).Methods: APPV717I Tg mice were randomly divided into a model group and icariin-treated (30 and 100 μmol/kg per day) groups. Learning-memory abilities were determined by Morris water maze and object recognition tests. Aβ contents were measured by enzyme-linked immunosorbent assays and immunohistochemistry. Amyloid plaques were detected by Congo red staining and Bielschowsky silver staining. The levels of expression of APP and β-site APP-cleaving enzyme 1 (BACE-1) were measured by western blotting and immunohistochemistry.Results: Ten-month-old Tg mice showed obvious learning-memory impairments, and significant increases in Aβ contents, amyloid plaques, and APP and BACE-1 levels in the hippocampus. The intragastric administration of icariin to Tg mice for 6 months (from 4 to 10 months of age) improved the learning-memory abilities and significantly decreased the Aβ contents, amyloid plaques, and APP and BACE-1 levels in the hippocampus.Conclusion: Icariin reduced the Aβ burden and amyloid plaque deposition in the hippocampus of APP transgenic mice by decreasing the APP and BACE-1 levels. These novel findings suggest that icariin may be a promising treatment in patients with AD.

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Section: Discussionsupporting

confidence: 77%

Icariin Decreases the Expression of APP and BACE-1 and Reduces the β-amyloid Burden in an APP Transgenic Mouse Model of Alzheimer's Disease

Zhang¹,

Shen²,

Chu³

et al. 2014

Int. J. Biol. Sci.

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“…MLC601 has shown both neuroprotective and neuroregenerative properties in several controlled studies of ischemic injury to the brain [15, 16, 17]. It has been shown that MLC601 is a possible modulator of amyloid precursor protein processing and has implications as a putative therapeutic strategy for the treatment of post-stroke dementia and Alzheimer disease [18]. In our recent study [7], we compared the efficacy and safety of MLC601 with cholinesterase inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of MLC601 in the Treatment of Mild Cognitive Impairment: A Pilot, Randomized, Double-Blind, Placebo-Controlled Study

Pakdaman

Harandi

Abbasi

et al. 2017

Dement Geriatr Cogn Disord Extra

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Background and Aim: Mild cognitive impairment (MCI) is characterized by declined cognitive function greater than that expected for a person’s age. The clinical significance of this condition is its possible progression to dementia. MLC601 is a natural neuroprotective medication that has shown promising effects in Alzheimer disease. Accordingly, we conducted this randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of MLC601 in MCI patients. Methods: Seventy-two patients with a diagnosis of MCI were recruited. The included participants were randomly assigned to groups to receive either MLC601 or placebo. An evaluation of global cognitive function was performed at baseline as well as at 3-month and 6-month follow-up visits. Global cognitive function was assessed by Mini-Mental State Examination (MMSE) and Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) scores. Efficacy was evaluated by comparing global function scores between the 2 groups during the study period. Safety assessment included adverse events (AEs) and abnormal laboratory results. Results: Seventy patients completed the study, 34 in the MLC601 group and 36 in the placebo group. The mean changes (±SD) in cognition scores over 6 months in the MLC601 group were –2.26 (±3.42) for the MMSE and 3.82 (±6.16) for the ADAS-cog; in the placebo group, they were –2.66 (±3.43) for the MMSE and 4.41 (±6.66) for the ADAS-cog. The cognition changes based on both MMSE and ADAS-cog scores were statistically significant between the placebo and the MLC601 group (p < 0.001). Only 5 patients (14.7%) reported minor AEs in the MLC601 group, the most commonly reported of which were gastrointestinal, none of them leading to patient withdrawal. Conclusion: MLC601 has shown promising efficacy and acceptable AEs in MCI patients.

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“…There is convergent evidence that overproduction, aberrant aggregation, and decreased elimination of different forms of amyloid beta protein are critical events in the pathogenesis of AD and, therefore, treatment development has focused on these processes [ 12 ]. In AD, APP is preferentially processed via the amyloidogenic pathway, producing large amounts of amyloid beta protein that forms the major constituent of senile plaques and tau-containing neurofibrillary tangles [ 22 ]. Since MLC601 has some neuroprotective effects, it is possible that it may exert its neuroprotective effects via the regulation of APP processing.…”

Section: Discussionmentioning

confidence: 99%

“…MLC601 is a possible modulator of APP processing. Lim et al [ 22 ] found that MLC601 induced a decrease in APP and enhanced the secreted forms of APPα release, suggesting that MLC601 may act by promoting the processing of APP via the nonamyloidogenic pathway.…”

Section: Discussionmentioning

confidence: 99%

“…MLC601 is a traditional Chinese medicine that has shown both neuroprotective and neurodegenerative properties in several controlled studies of ischemic injury to the brain [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. However, it has been shown that MLC601 is a possible modulator of amyloid precursor protein (APP) processing and has implications as a putative therapeutic strategy for the treatment of poststroke dementia and AD [ 22 ]. In a clinical trial study, MLC601 showed favorable tolerability and encouraging effectiveness on cognitive function in AD patients during 18 months of treatment when compared to rivastigmine [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

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Effectiveness and Safety of MLC601 in the Treatment of Mild to Moderate Alzheimer's Disease: A Multicenter, Randomized Controlled Trial

Pakdaman

Harandi

Hatamian

et al. 2015

Dement Geriatr Cogn Disord Extra

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Background: MLC601 is a possible modulator of amyloid precursor protein processing, and in a clinical trial study MLC601 showed some effectiveness in cognitive function in Alzheimer's disease (AD) patients. We aimed to evaluate the effectiveness and safety of MLC601 in the treatment of mild to moderate AD as compared to 3 approved cholinesterase inhibitors (ChEIs) including donepezil, rivastigmine and galantamine. Methods: In a multicenter, nonblinded, randomized controlled trial, 264 volunteers with AD were randomly divided into 4 groups of 66; groups 1, 2, 3 and 4 received donepezil, rivastigmine, MLC601 and galantamine, respectively. Subjects underwent a clinical diagnostic interview and a cognitive/functional battery including the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog). Patients were visited every 4 months, and the score of cognition was recorded by the neurologists. Results: There were no significant differences in age, sex, marital status and baseline score of cognition among the 4 groups. In total, 39 patients (14.7%) left the study. Trend of cognition changes based on the modifications over the time for MMSE and ADAS-cog scores did not differ significantly among groups (p = 0.92 for MMSE and p = 0.87 for ADAS-Cog). Conclusion: MLC601 showed a promising safety profile and also efficacy compared to 3 FDA-approved ChEIs.

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NeuroAiD® (MLC601) and Amyloid Precursor Protein Processing

Cited by 13 publications

References 98 publications

Icariin Decreases the Expression of APP and BACE-1 and Reduces the β-amyloid Burden in an APP Transgenic Mouse Model of Alzheimer's Disease

Icariin Decreases the Expression of APP and BACE-1 and Reduces the β-amyloid Burden in an APP Transgenic Mouse Model of Alzheimer's Disease

Efficacy and Safety of MLC601 in the Treatment of Mild Cognitive Impairment: A Pilot, Randomized, Double-Blind, Placebo-Controlled Study

Effectiveness and Safety of MLC601 in the Treatment of Mild to Moderate Alzheimer's Disease: A Multicenter, Randomized Controlled Trial

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