Dementia, including Alzheimer’s disease, the 21^st Century epidemic, is one of the most signifcant social and health crises which has currently afficted nearly 44 million patients worldwide and about new 7.7 million ...Dementia, including Alzheimer’s disease, the 21^st Century epidemic, is one of the most signifcant social and health crises which has currently afficted nearly 44 million patients worldwide and about new 7.7 million cases are reported every year. This portrays the unmet need towards better understanding of Alzheimer’s disease pathomechanisms and related research towards more effective treatment strategies. The review thus comprehensively addresses Alzheimer’s disease pathophysiology with an insight of underlying multicascade pathway and elaborates possible therapeutic targets- particularly anti-amyloid approaches, anti-tau approaches, acetylcholinesterase inhibitors, glutamatergic system modifiers, immunotherapy, anti-nflammatory targets, antioxidants, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors and insulin. In spite of extensive research leading to identification of newer targets and potent drugs, complete cure of Alzheimer’s disease appears to be an unreached holy grail. This can be attributed to their ineffective delivery across blood brain barrier and ultimately to the brain. With this understanding, researchers are now focusing on development of drug delivery systems to be delivered via suitable route that can circumvent blood brain barrier effectively with enhanced patient compliance. In this context, we have summarized current drug delivery strategies by oral, transdermal, intravenous, intranasal and other miscellaneous routes and have accentuated the future standpoint towards promising therapy ultimately eading to Alzheimer’s disease cure.展开更多
Current hypotheses of pathogenesis of neuronal degeneration in Alzheimer's disease (AD) have been proposed, including formation of free radicals, oxidative stress, mitochondrial dysfunction, inflammatory processes...Current hypotheses of pathogenesis of neuronal degeneration in Alzheimer's disease (AD) have been proposed, including formation of free radicals, oxidative stress, mitochondrial dysfunction, inflammatory processes, genetic factors, environmental impact factors, apoptosis, and so on. Especially, oxidative stress plays an essential role in AD pathogenesis by the function of linking agent. Oxidative stress in AD mainly includes lipid peroxidation, protein oxidation and DNA oxidation. Lipid peroxidation plays a key role in the development and progression of AD. Protein oxidation is an important mechanism in AD. Oxidative damage to DNA may plays an important role in aging and AD.展开更多
Objective To learn the effect of omemtum transposition to the brain of patients with Alzheimer’s disease. Methods Ten consecutive patients, aged 58-81 years old, underwent graft of their elongated pedicled omentum on...Objective To learn the effect of omemtum transposition to the brain of patients with Alzheimer’s disease. Methods Ten consecutive patients, aged 58-81 years old, underwent graft of their elongated pedicled omentum onto their left frontal-temperal-parietal cerebral cortex. Those patients, who had more than five years of dementia with low mini mental-state examination (MMSE) scores of 2-15, were diagnosed by a neurologist. All subjects underwent single photon evoked computer tomography (SPECT) pre- and post-operatively. SPECT results were analyzed semi-quantitatively by calculation of the left/right radioactivity counts symmetry index (Si). The patients were followed up to one year. The outcome was evaluated by the neurologist with a modified scale of activities of daily living (mADL) as well as the MMSE. Results Three months following the surgery, the Si of SPECT increased from (98.7±1.9)% to (103.9±2.3)% (P=0.0307). The neurological and neuropsychological testing scores increased insignificantly during the follow-up period. By the one year, the MMSE score rose from 8.7±1.4 to 10.7±1.8(P>0.05), while the mADL from 13.3±1.8 to 16.9±2.0 (P>0.05). One of the patients suffered a heart attack, two had epileptic episodes postoperatively. Conclusion We believe that omental transposition to the brain augments cerebral blood flow, which might be helpful to decelerate the processing of Alzheimer’s disease. However, it is still a potentially risky procedure for the elderly.展开更多
OBJECTIVE: To explore the mechanism of reinforcing kidney-essence, removing phlegm, and promoting mental therapy in treating Alzheimer's disease (AD). METHODS: Sixty patients with AD in Wuhan No.1 Hospital of Trad...OBJECTIVE: To explore the mechanism of reinforcing kidney-essence, removing phlegm, and promoting mental therapy in treating Alzheimer's disease (AD). METHODS: Sixty patients with AD in Wuhan No.1 Hospital of Traditional Chinese Medicine for Geriatrics from May 2009 to April 2011 were randomly divided into two groups, with 30 in each group. Patients in Bushenhuatanyizhi group (BHY group) took BHY instant granules (6 g, twice per day). Patients in the control group took piracetam (0.8 g, 3 times per day). There were twelve weeks in a course. Changes in the mini-mental state examination (MMSE) score and Activity of Daily Living Scale (ADL) score were analyzed before and after treatment. RESULTS: MMSE scores in the two groups in-creased and ADL scores decreased after treatment, compared with those before treatment (both P< 0.05).The total effective rate was 86.67% in the BHY group (10 very effective, 13 effective, 7 non-responsive). The control group was 57.69% (5 very effective, 16 effective, 9 non-responsive) (P<0.05). Superoxide dismutase levels were increased, lipid peroxide and triglyceride levels decreased after treatment in the BHY group as compared with the control group. CONCLUSION: Reinforcing kidney-essence, removing phlegm, and promoting mental therapy can improve cognitive function and daily life of AD patients. The mechanism of the therapy might be related to improving blood fat, scavenging free radicals, and inhibiting lipid peroxides.展开更多
Although advances have been made, chemotherapy for chronic, multifactorial diseases such as cancers, Alzheimer's disease, cardiovascular diseases and diabetes is far from satisfactory. Agents with different mechan...Although advances have been made, chemotherapy for chronic, multifactorial diseases such as cancers, Alzheimer's disease, cardiovascular diseases and diabetes is far from satisfactory. Agents with different mechanisms of action are required. The botanic compound berberine(BBR) has been used as an over-the-counter antibacterial for diarrhea in China for many decades. Recent clinical studies have shown that BBR may be therapeutic in various types of chronic diseases. This review addresses BBR's molecular mechanisms of action and clinical efficacy and safety in patients with type 2 diabetes, hyperlipidemia, heart diseases, cancers and inflammation. One of the advantages of BBR is its multiple-target effects in each of these diseases. The therapeutic efficacy of BBR may reflect a synergistic regulation of these targets, resulting in a comprehensive effect against these various chronic disorders. The safety of BBR may be due to its harmonious distribution into those targets. Although the single-target concept is still the principle for drug discovery and research, this review emphasizes the concept of a multiple target strategy, which may be an important approach toward the successful treatment of multifactorial chronic diseases.展开更多
Polymerization of amyloid-β peptide （Aβ） into amyloid fibrils is a critical step in the pathogenesis of Alzheimer＇s disease （AD）. Inhibition of Aβ aggregation and destabilization of preformed Aβ fibrils have ...Polymerization of amyloid-β peptide （Aβ） into amyloid fibrils is a critical step in the pathogenesis of Alzheimer＇s disease （AD）. Inhibition of Aβ aggregation and destabilization of preformed Aβ fibrils have promising effects against AD and have been used in clinic trials. Herein, we demonstrate, for the first time, the application of WS2 nanosheets, to not only effectively inhibit Aβ aggregation, but also dissociate preformed Aβ aggregates upon near infrared （NIR） irradiation. Additionally, the biocompatible WS2 nanosheets possess the ability to cross the blood-brain barrier （BBB） to overcome the limitations of most previously reported Aβ inhibitors. Through van der Waals and electrostatic interactions between Aβ40 and WS2, Aβ40 monomers can be selectively adsorbed on the surface of the nanosheet to inhibit the Aβ40 aggregation process. Intriguingly, the unique high NIR absorption property of WS2 enables amyloid aggregates to be dissolved upon NIR irradiation. These results will promote biological applications of WS2 and provide new insight into the design of multifunctional nanomaterials for AD treatment.展开更多
OBJECTIVE:To study the efficacy and safety of combined Traditional Chinese Medicine(TCM) therapy based on nourishing marrow to improve intellect and reinforcing Qi to activate bloodon mild to moderate Alzheimer's ...OBJECTIVE:To study the efficacy and safety of combined Traditional Chinese Medicine(TCM) therapy based on nourishing marrow to improve intellect and reinforcing Qi to activate bloodon mild to moderate Alzheimer's disease(AD).METHODS:Sixty-six patients with AD,whoseMini-Mental State Examination(MMSE) score were from 10-24,were randomized equally into an intervention group and a control group.The control group was given Aricept(5 mg,once daily).The intervention group was further divided into Yang-Qi deficiency(n = 18) and of Yin-Qi deficiency(n = 15)subgroups.Patients in the Yang-Qi deficiency group were intravenously administered Shenfu injection,60 mL,and deproteinized calf blood injection(DCBl),1.2 g,once daily.The Yin-Qi deficiency group was given Shenmai injection,60 mL,and DCBl,1.2 g,once daily.Each course lasted 21 days.RESULTS:Compared with the control group and with pre-treatment in the same group,MMSE,clinical dementia rating,and activities of daily living scale scores in the intervention group were significantly improved(all P<0.05).These metrics mildly improved in the control group compared with before treatment(P>0.05).No adverse effects were observed in any group during treatment.CONCLUSION:We found that combined TCM therapy is effective and safe for managing mild to moderate AD.展开更多
文摘Dementia, including Alzheimer’s disease, the 21^st Century epidemic, is one of the most signifcant social and health crises which has currently afficted nearly 44 million patients worldwide and about new 7.7 million cases are reported every year. This portrays the unmet need towards better understanding of Alzheimer’s disease pathomechanisms and related research towards more effective treatment strategies. The review thus comprehensively addresses Alzheimer’s disease pathophysiology with an insight of underlying multicascade pathway and elaborates possible therapeutic targets- particularly anti-amyloid approaches, anti-tau approaches, acetylcholinesterase inhibitors, glutamatergic system modifiers, immunotherapy, anti-nflammatory targets, antioxidants, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors and insulin. In spite of extensive research leading to identification of newer targets and potent drugs, complete cure of Alzheimer’s disease appears to be an unreached holy grail. This can be attributed to their ineffective delivery across blood brain barrier and ultimately to the brain. With this understanding, researchers are now focusing on development of drug delivery systems to be delivered via suitable route that can circumvent blood brain barrier effectively with enhanced patient compliance. In this context, we have summarized current drug delivery strategies by oral, transdermal, intravenous, intranasal and other miscellaneous routes and have accentuated the future standpoint towards promising therapy ultimately eading to Alzheimer’s disease cure.
文摘Current hypotheses of pathogenesis of neuronal degeneration in Alzheimer's disease (AD) have been proposed, including formation of free radicals, oxidative stress, mitochondrial dysfunction, inflammatory processes, genetic factors, environmental impact factors, apoptosis, and so on. Especially, oxidative stress plays an essential role in AD pathogenesis by the function of linking agent. Oxidative stress in AD mainly includes lipid peroxidation, protein oxidation and DNA oxidation. Lipid peroxidation plays a key role in the development and progression of AD. Protein oxidation is an important mechanism in AD. Oxidative damage to DNA may plays an important role in aging and AD.
文摘Objective To learn the effect of omemtum transposition to the brain of patients with Alzheimer’s disease. Methods Ten consecutive patients, aged 58-81 years old, underwent graft of their elongated pedicled omentum onto their left frontal-temperal-parietal cerebral cortex. Those patients, who had more than five years of dementia with low mini mental-state examination (MMSE) scores of 2-15, were diagnosed by a neurologist. All subjects underwent single photon evoked computer tomography (SPECT) pre- and post-operatively. SPECT results were analyzed semi-quantitatively by calculation of the left/right radioactivity counts symmetry index (Si). The patients were followed up to one year. The outcome was evaluated by the neurologist with a modified scale of activities of daily living (mADL) as well as the MMSE. Results Three months following the surgery, the Si of SPECT increased from (98.7±1.9)% to (103.9±2.3)% (P=0.0307). The neurological and neuropsychological testing scores increased insignificantly during the follow-up period. By the one year, the MMSE score rose from 8.7±1.4 to 10.7±1.8(P>0.05), while the mADL from 13.3±1.8 to 16.9±2.0 (P>0.05). One of the patients suffered a heart attack, two had epileptic episodes postoperatively. Conclusion We believe that omental transposition to the brain augments cerebral blood flow, which might be helpful to decelerate the processing of Alzheimer’s disease. However, it is still a potentially risky procedure for the elderly.
基金Supported by the State Key Program of National Natural Science of China(No.81130064)Doctoral Fund of Ministry of Education of China(No.20094230110001)National Natural Science Foundation of China(No.30901937)
文摘OBJECTIVE: To explore the mechanism of reinforcing kidney-essence, removing phlegm, and promoting mental therapy in treating Alzheimer's disease (AD). METHODS: Sixty patients with AD in Wuhan No.1 Hospital of Traditional Chinese Medicine for Geriatrics from May 2009 to April 2011 were randomly divided into two groups, with 30 in each group. Patients in Bushenhuatanyizhi group (BHY group) took BHY instant granules (6 g, twice per day). Patients in the control group took piracetam (0.8 g, 3 times per day). There were twelve weeks in a course. Changes in the mini-mental state examination (MMSE) score and Activity of Daily Living Scale (ADL) score were analyzed before and after treatment. RESULTS: MMSE scores in the two groups in-creased and ADL scores decreased after treatment, compared with those before treatment (both P< 0.05).The total effective rate was 86.67% in the BHY group (10 very effective, 13 effective, 7 non-responsive). The control group was 57.69% (5 very effective, 16 effective, 9 non-responsive) (P<0.05). Superoxide dismutase levels were increased, lipid peroxide and triglyceride levels decreased after treatment in the BHY group as compared with the control group. CONCLUSION: Reinforcing kidney-essence, removing phlegm, and promoting mental therapy can improve cognitive function and daily life of AD patients. The mechanism of the therapy might be related to improving blood fat, scavenging free radicals, and inhibiting lipid peroxides.
基金supported by the National Mega-Project for Drug Research&Development,China(to Jiang Jian Dong)
文摘Although advances have been made, chemotherapy for chronic, multifactorial diseases such as cancers, Alzheimer's disease, cardiovascular diseases and diabetes is far from satisfactory. Agents with different mechanisms of action are required. The botanic compound berberine(BBR) has been used as an over-the-counter antibacterial for diarrhea in China for many decades. Recent clinical studies have shown that BBR may be therapeutic in various types of chronic diseases. This review addresses BBR's molecular mechanisms of action and clinical efficacy and safety in patients with type 2 diabetes, hyperlipidemia, heart diseases, cancers and inflammation. One of the advantages of BBR is its multiple-target effects in each of these diseases. The therapeutic efficacy of BBR may reflect a synergistic regulation of these targets, resulting in a comprehensive effect against these various chronic disorders. The safety of BBR may be due to its harmonious distribution into those targets. Although the single-target concept is still the principle for drug discovery and research, this review emphasizes the concept of a multiple target strategy, which may be an important approach toward the successful treatment of multifactorial chronic diseases.
基金This work was supported by the National Basic Research Program of China （Nos. 2011CB936004 and 2012CB720602）, and the National Natural Science Foundation of China （Nos. 21210002, 91213302, 21431007, and 91413111）.
文摘Polymerization of amyloid-β peptide （Aβ） into amyloid fibrils is a critical step in the pathogenesis of Alzheimer＇s disease （AD）. Inhibition of Aβ aggregation and destabilization of preformed Aβ fibrils have promising effects against AD and have been used in clinic trials. Herein, we demonstrate, for the first time, the application of WS2 nanosheets, to not only effectively inhibit Aβ aggregation, but also dissociate preformed Aβ aggregates upon near infrared （NIR） irradiation. Additionally, the biocompatible WS2 nanosheets possess the ability to cross the blood-brain barrier （BBB） to overcome the limitations of most previously reported Aβ inhibitors. Through van der Waals and electrostatic interactions between Aβ40 and WS2, Aβ40 monomers can be selectively adsorbed on the surface of the nanosheet to inhibit the Aβ40 aggregation process. Intriguingly, the unique high NIR absorption property of WS2 enables amyloid aggregates to be dissolved upon NIR irradiation. These results will promote biological applications of WS2 and provide new insight into the design of multifunctional nanomaterials for AD treatment.
基金the Fund of Science and Technology Project of Guangdong Province(the Mechanism Study for the Therapy of Jianpiyishenfangin Treating Glucocorticoid Tolerance MyastheniaGravis,No.2011B090400118)
文摘OBJECTIVE:To study the efficacy and safety of combined Traditional Chinese Medicine(TCM) therapy based on nourishing marrow to improve intellect and reinforcing Qi to activate bloodon mild to moderate Alzheimer's disease(AD).METHODS:Sixty-six patients with AD,whoseMini-Mental State Examination(MMSE) score were from 10-24,were randomized equally into an intervention group and a control group.The control group was given Aricept(5 mg,once daily).The intervention group was further divided into Yang-Qi deficiency(n = 18) and of Yin-Qi deficiency(n = 15)subgroups.Patients in the Yang-Qi deficiency group were intravenously administered Shenfu injection,60 mL,and deproteinized calf blood injection(DCBl),1.2 g,once daily.The Yin-Qi deficiency group was given Shenmai injection,60 mL,and DCBl,1.2 g,once daily.Each course lasted 21 days.RESULTS:Compared with the control group and with pre-treatment in the same group,MMSE,clinical dementia rating,and activities of daily living scale scores in the intervention group were significantly improved(all P<0.05).These metrics mildly improved in the control group compared with before treatment(P>0.05).No adverse effects were observed in any group during treatment.CONCLUSION:We found that combined TCM therapy is effective and safe for managing mild to moderate AD.
