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Combined metabolic ...
Combined metabolic activators improve cognitive functions in Alzheimer's disease patients: a randomised, double-blinded, placebo-controlled phase-II trial
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- Yulug, B. (författare)
- Alanya Alaaddin Keykubat Univ, Fac Med, Dept Neurol & Neurosci, Antalya, Turkey.
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- Altay, Özlem (författare)
- KTH,Science for Life Laboratory, SciLifeLab,Systembiologi
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- Li, Xiangyu (författare)
- KTH,Systembiologi,Science for Life Laboratory, SciLifeLab
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- Hanoglu, L. (författare)
- Istanbul Medipol Universitesi,Istanbul Medipol Univ, Fac Med, Dept Neurol, Istanbul, Turkey.
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- Cankaya, S. (författare)
- Alanya Alaaddin Keykubat Univ, Fac Med, Dept Neurol & Neurosci, Antalya, Turkey.
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- Lam, S. (författare)
- King's College London,Kings Coll London, Fac Dent, Ctr Host Microbiome Interact, Oral & Craniofacial Sci, London, England.
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- Velioglu, H. A. (författare)
- Istanbul Medipol Universitesi,Karolinska Institutet,Atatürk Üniversitesi,Atatürk University,Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Istanbul Medipol Univ, Funct Imaging & Cognit Affect Neurosci Lab, Istanbul, Turkey.,Ataturk Univ, Fac Med, Dept Med Pharmacol, Erzurum, Turkey.
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- Yang, Hong (författare)
- KTH,Science for Life Laboratory, SciLifeLab,Systembiologi
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- Coskun, E. (författare)
- Istanbul Medipol Universitesi,Istanbul Medipol Univ, Fac Med, Dept Neurol, Istanbul, Turkey.
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- Idil, E. (författare)
- Alanya Alaaddin Keykubat Univ, Fac Med, Dept Neurol & Neurosci, Antalya, Turkey.
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- Nogaylar, R. (författare)
- Alanya Alaaddin Keykubat Univ, Fac Med, Dept Neurol & Neurosci, Antalya, Turkey.
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- Ozsimsek, A. (författare)
- Alanya Alaaddin Keykubat Univ, Fac Med, Dept Neurol & Neurosci, Antalya, Turkey.
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- Bayram, C. (författare)
- Atatürk Üniversitesi,Atatürk University,Ataturk Univ, Fac Med, Dept Med Pharmacol, Erzurum, Turkey.
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- Bolat, I. (författare)
- Atatürk Üniversitesi,Atatürk University,Ataturk Univ, Vet Fac, Dept Pathol, Erzurum, Turkey.
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- Oner, S. (författare)
- Erzurum Teknik Üniversitesi,Erzurum Technical University,Erzurum Tech Univ, Fac Sci, Dept Mol Biol & Genet, Erzurum, Turkey.
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- Tozlu, O. O. (författare)
- Erzurum Teknik Üniversitesi,Erzurum Technical University,Erzurum Tech Univ, Fac Sci, Dept Mol Biol & Genet, Erzurum, Turkey.
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- Arslan, M. E. (författare)
- Erzurum Teknik Üniversitesi,Erzurum Technical University,Erzurum Tech Univ, Fac Sci, Dept Mol Biol & Genet, Erzurum, Turkey.
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Hacimuftuoglu, A. (författare)
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- Yildirim, S. (författare)
- Atatürk Üniversitesi,Atatürk University,Ataturk Univ, Vet Fac, Dept Pathol, Erzurum, Turkey.
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- Arif, Muhammad (författare)
- KTH,Systembiologi,Science for Life Laboratory, SciLifeLab
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- Shoaie, Saeed, 1985 (författare)
- KTH,Science for Life Laboratory, SciLifeLab,Systembiologi,Kings Coll London, Fac Dent, Ctr Host Microbiome Interact, Oral & Craniofacial Sci, London, England.
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- Zhang, C. (författare)
- KTH,Science for Life Laboratory, SciLifeLab,Systembiologi,Zhengzhou Univ, Sch Pharmaceut Sci, Zhengzhou, Peoples R China.
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- Nielsen, Jens B, 1962 (författare)
- Chalmers tekniska högskola,Chalmers University of Technology,Chalmers Univ Technol, Dept Biol & Biol Engn, Gothenburg, Sweden.
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- Turkez, H. (författare)
- Atatürk Üniversitesi,Atatürk University,Ataturk Univ, Fac Med, Dept Med Biol, Erzurum, Turkey.
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- Borén, Jan, 1963 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg,Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Mol & Clin Med, Gothenburg, Sweden.
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- Uhlén, Mathias (författare)
- KTH,Science for Life Laboratory, SciLifeLab,Systembiologi
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- Mardinoglu, Adil, 1982 (författare)
- KTH,Science for Life Laboratory, SciLifeLab,Systembiologi,Kings Coll London, Fac Dent, Ctr Host Microbiome Interact, Oral & Craniofacial Sci, London, England.
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Alanya Alaaddin Keykubat Univ, Fac Med, Dept Neurol & Neurosci, Antalya, Turkey Science for Life Laboratory, SciLifeLab (creator_code:org_t)
- 2023-01-26
- 2023
- Engelska.
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Ingår i: Translational Neurodegeneration. - : Springer Science and Business Media LLC. - 2047-9158. ; 12:1
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https://research.cha... (primary) (free)
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https://doi.org/10.1...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Nyckelord
- Alzheimer's disease
- Combined metabolic activators
- Multi-omics
- Systems
- biology
- Systems medicine
- transforming growth-factor-beta-1 gene
- growth-factor
- kynurenine
- pathway
- glucose-metabolism
- n-acetylcysteine
- oxidative stress
- mouse
- model
- brain
- beta
- receptor
- Neurosciences & Neurology
- Combined metabolic activators
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Yulug, B.
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Altay, Özlem
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Li, Xiangyu
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Hanoglu, L.
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Cankaya, S.
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Lam, S.
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visa fler...
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Velioglu, H. A.
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Yang, Hong
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Coskun, E.
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Idil, E.
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Nogaylar, R.
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Ozsimsek, A.
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Bayram, C.
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Bolat, I.
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Oner, S.
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Tozlu, O. O.
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Arslan, M. E.
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Hacimuftuoglu, A ...
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Yildirim, S.
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Arif, Muhammad
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Shoaie, Saeed, 1 ...
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Zhang, C.
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Nielsen, Jens B, ...
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Turkez, H.
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Borén, Jan, 1963
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Uhlén, Mathias
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Mardinoglu, Adil ...
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Neurologi
- Artiklar i publikationen
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Translational Ne ...
- Av lärosätet
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Göteborgs universitet
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Chalmers tekniska högskola
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Kungliga Tekniska Högskolan
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Karolinska Institutet