Combined metabolic activators improve metabolic functions in the animal models of neurodegenerative diseases

Basit Öğe Kaydı
dc.authorid0000-0003-4292-5717
dc.authorid0000-0003-1028-6703
dc.contributor.authorTürkez, Hasan
dc.contributor.authorAltay, Özlem
dc.contributor.authorYıldırım, Serkan
dc.contributor.authorLi, Xiangyu
dc.contributor.authorYang, Hong
dc.contributor.authorBayram, Cemil
dc.contributor.authorBolat, İsmail
dc.contributor.authorÖner, Sena
dc.contributor.authorÖzdemir Tozlu, Özlem
dc.contributor.authorArslan, Mehmet Enes
dc.contributor.authorArif, Muhammad
dc.contributor.authorYuluğ, Burak
dc.contributor.authorHanoğlu, Lütfü
dc.contributor.authorÇankaya, Şeyda
dc.contributor.authorLam, Simon
dc.contributor.authorVelioğlu, Halil Aziz
dc.contributor.authorCoşkun, Ebru
dc.contributor.authorİdil, Ezgi
dc.contributor.authorNogaylar, Rahim
dc.contributor.authorÖzşimşek, Ahmet
dc.contributor.authorHacımüftüoğlu, Ahmet
dc.contributor.authorShoaie, Saeed
dc.contributor.authorZhang, Cheng
dc.contributor.authorNielsen, Jens
dc.contributor.authorBorén, Jan
dc.contributor.authorUhlén, Mathias
dc.contributor.authorMardinoğlu, Adil
dc.date.accessioned2023-01-06T07:23:02Z
dc.date.available2023-01-06T07:23:02Z
dc.date.issued2023
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Nöroloji Ana Bilim Dalı
dc.description.abstractBackground: Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), are associated with metabolic abnormalities. Integrative analysis of human clinical data and animal studies have contributed to a better understanding of the molecular and cellular pathways involved in the progression of NDDs. Previously, we have reported that the combined metabolic activators (CMA), which include the precursors of nicotinamide adenine dinucleotide and glutathione can be utilized to alleviate metabolic disorders by activating mitochondrial metabolism. Methods: We first analysed the brain transcriptomics data from AD patients and controls using a brain-specific genome-scale metabolic model (GEM). Then, we investigated the effect of CMA administration in animal models of AD and PD. We evaluated pathological and immunohistochemical findings of brain and liver tissues. Moreover, PD rats were tested for locomotor activity and apomorphine-induced rotation. Findings: Analysis of transcriptomics data with GEM revealed that mitochondrial dysfunction is involved in the underlying molecular pathways of AD. In animal models of AD and PD, we showed significant damage in the high-fat diet groups' brain and liver tissues compared to the chow diet. The histological analyses revealed that hyperemia, degeneration and necrosis in neurons were improved by CMA administration in both AD and PD animal models. These findings were supported by immunohistochemical evidence of decreased immunoreactivity in neurons. In parallel to the improvement in the brain, we also observed dramatic metabolic improvement in the liver tissue. CMA administration also showed a beneficial effect on behavioural functions in PD rats. Interpretation: Overall, we showed that CMA administration significantly improved behavioural scores in parallel with the neurohistological outcomes in the AD and PD animal models and is a promising treatment for improving the metabolic parameters and brain functions in NDDs.
dc.description.sponsorshipPoLiMeR Innovative Training Network ; SNIC ; ScandiBio Therapeutics ; ScandiBio Therapeutics and Knut ; Knut och Alice Wallenbergs Stiftelseen_US
dc.identifier.citationTürkez, H., Altay, Ö., Yıldırım, S., Li, X., Yang, H., Bayram, C. ... Mardinoğlu, A. (2023). Combined metabolic activators improve metabolic functions in the animal models of neurodegenerative diseases. Life Sciences, 314. https://dx.doi.org/10.1016/j.lfs.2022.121325
dc.identifier.doi10.1016/j.lfs.2022.121325
dc.identifier.issn0024-3205
dc.identifier.issn1879-0631
dc.identifier.pmid36581096
dc.identifier.scopus2-s2.0-85145161292
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://dx.doi.org/10.1016/j.lfs.2022.121325
dc.identifier.urihttps://hdl.handle.net/20.500.12511/10251
dc.identifier.volume314
dc.identifier.wos000915897400001en_US
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorHanoğlu, Lütfü
dc.institutionauthorCoşkun, Ebru
dc.language.isoen
dc.publisherElsevier Inc.
dc.relation.ispartofLife Sciencesen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectNeurodegenerative Diseases
dc.subjectCombined Metabolic Activators
dc.subjectGenome-Scale Metabolic Model
dc.subjectAnimal Model
dc.titleCombined metabolic activators improve metabolic functions in the animal models of neurodegenerative diseases
dc.typeArticle

Dosyalar

Orijinal paket
Listeleniyor 1 - 1 / 1
Küçük Resim
İsim:
Hanoglu-Lutfu-2022.pdf
Boyut:
10.26 MB
Biçim:
Adobe Portable Document Format
Açıklama:
Tam Metin / Full Text
İndir
Lisans paketi
Listeleniyor 1 - 1 / 1
Küçük Resim Yok
İsim:
license.txt
Boyut:
1.44 KB
Biçim:
Item-specific license agreed upon to submission
Açıklama:
İndir

Koleksiyon

Makale Koleksiyonu
PubMed İndeksli Yayınlar Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu
WoS İndeksli Yayınlar Koleksiyonu