Cinnamon, is an exotic spice and a major constituent of our food which is commonly used in different areas of the world for the treatment of various diseases (Kawatra et al., 2015). Besides 让s anti-inflammatory, anti...Cinnamon, is an exotic spice and a major constituent of our food which is commonly used in different areas of the world for the treatment of various diseases (Kawatra et al., 2015). Besides 让s anti-inflammatory, anti-diabetic and anti-cancer properties, cinnamon also exerts strong brain protective and pro-cogrdtive effects in various models of neurodegeneration (Kawatra et al., 2015;Kelestemur et al., 2016)(Figure 1).展开更多
It has been already shown that Parkinson’s disease (PD) is characterized by a prominent degeneration in substantia nigra (SN) neurons. Growing evidence suggests that there is a latent period of PD associated with sli...It has been already shown that Parkinson’s disease (PD) is characterized by a prominent degeneration in substantia nigra (SN) neurons. Growing evidence suggests that there is a latent period of PD associated with slight non-motor findings such as olfactory dysfunction (Dickson et al., 2018). However, the potential biomarker role of olfactory dysfunction in PD has been a topic of great interest in the last years (Raskin et al., 1990;Dickson et al., 2018). The classical hypothesis of Braak suggests that PD begins as a synucleinopathy in the lower brainstem or in the olfactory bulb (OB) that progresses rostrally to the SN and amygdala to cause parkinsonism at a later stage of the disease (Burke et al., 2008).展开更多
Background Alzheimer’s disease(AD)is associated with metabolic abnormalities linked to critical elements of neurodegeneration.We recently administered combined metabolic activators(CMA)to the AD rat model and observe...Background Alzheimer’s disease(AD)is associated with metabolic abnormalities linked to critical elements of neurodegeneration.We recently administered combined metabolic activators(CMA)to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals.CMA promotes mitochondrial fatty acid uptake from the cytosol,facilitates fatty acid oxidation in the mitochondria,and alleviates oxidative stress.Methods Here,we designed a randomised,double-blinded,placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients.One-dose CMA included 12.35 g L-serine(61.75%),1 g nicotinamide riboside(5%),2.55 g N-acetyl-L-cysteine(12.75%),and 3.73 g L-carnitine tartrate(18.65%).AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84.The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms.The secondary aim of this study was to evaluate the safety and tolerability of CMA.A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients.Results We showed a significant decrease of AD Assessment Scale-cognitive subscale(ADAS-Cog)score on day 84 vs day 0(P=0.00001,29%improvement)in the CMA group.Moreover,there was a significant decline(P=0.0073)in ADAS-Cog scores(improvement of cognitive functions)in the CMA compared to the placebo group in patients with higher ADAS-Cog scores.Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis.Moreover,the plasma levels of proteins and metabolites associated with NAD+and glutathione metabolism were significantly improved after CMA treatment.Conclusion Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics,metabolomics,proteomics and imaging analysis.展开更多
文摘Cinnamon, is an exotic spice and a major constituent of our food which is commonly used in different areas of the world for the treatment of various diseases (Kawatra et al., 2015). Besides 让s anti-inflammatory, anti-diabetic and anti-cancer properties, cinnamon also exerts strong brain protective and pro-cogrdtive effects in various models of neurodegeneration (Kawatra et al., 2015;Kelestemur et al., 2016)(Figure 1).
文摘It has been already shown that Parkinson’s disease (PD) is characterized by a prominent degeneration in substantia nigra (SN) neurons. Growing evidence suggests that there is a latent period of PD associated with slight non-motor findings such as olfactory dysfunction (Dickson et al., 2018). However, the potential biomarker role of olfactory dysfunction in PD has been a topic of great interest in the last years (Raskin et al., 1990;Dickson et al., 2018). The classical hypothesis of Braak suggests that PD begins as a synucleinopathy in the lower brainstem or in the olfactory bulb (OB) that progresses rostrally to the SN and amygdala to cause parkinsonism at a later stage of the disease (Burke et al., 2008).
基金funding provided by Royal Institute of Technology.This work was financially supported by ScandiBio Therapeutics and Knut and Alice Wallenberg Foundation(72110).
文摘Background Alzheimer’s disease(AD)is associated with metabolic abnormalities linked to critical elements of neurodegeneration.We recently administered combined metabolic activators(CMA)to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals.CMA promotes mitochondrial fatty acid uptake from the cytosol,facilitates fatty acid oxidation in the mitochondria,and alleviates oxidative stress.Methods Here,we designed a randomised,double-blinded,placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients.One-dose CMA included 12.35 g L-serine(61.75%),1 g nicotinamide riboside(5%),2.55 g N-acetyl-L-cysteine(12.75%),and 3.73 g L-carnitine tartrate(18.65%).AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84.The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms.The secondary aim of this study was to evaluate the safety and tolerability of CMA.A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients.Results We showed a significant decrease of AD Assessment Scale-cognitive subscale(ADAS-Cog)score on day 84 vs day 0(P=0.00001,29%improvement)in the CMA group.Moreover,there was a significant decline(P=0.0073)in ADAS-Cog scores(improvement of cognitive functions)in the CMA compared to the placebo group in patients with higher ADAS-Cog scores.Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis.Moreover,the plasma levels of proteins and metabolites associated with NAD+and glutathione metabolism were significantly improved after CMA treatment.Conclusion Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics,metabolomics,proteomics and imaging analysis.
