Geri Dön

Modulation of endoplasmic reticulum-mitochondria interactions by tauopathy-associated mutations

Başlık çevirisi mevcut değil.

  1. Tez No: 519548
  2. Yazar: SAFİYE SERDENGEÇTİ
  3. Danışmanlar: Dr. DAWN LAU
  4. Tez Türü: Yüksek Lisans
  5. Konular: Nöroloji, Neurology
  6. Anahtar Kelimeler: Belirtilmemiş.
  7. Yıl: 2016
  8. Dil: İngilizce
  9. Üniversite: King's College London
  10. Enstitü: Yurtdışı Enstitü
  11. Ana Bilim Dalı: Belirtilmemiş.
  12. Bilim Dalı: Belirtilmemiş.
  13. Sayfa Sayısı: 46

Özet

Özet yok.

Özet (Çeviri)

Neurodegenerative diseases are a major cause of disability in aging population worldwide with a wide spectrum of disorders afflicting not only people's physical and mental health but also having a high cost for economy globally. Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis in association with frontotemporal dementia (ALS/FTD) are the most common forms of neurodegeneration. All of these diseases are characterised by disruptions of many cellular processes and functions in different forms throughout the brain. Even though these diseases have clinically distinct progressive degeneration and impact different regions of the brain, several studies demonstrated that many of the functions perturbed in these neurodegenerative diseases seem to be regulated by interactions of mitochondria with specific regions of the endoplasmic reticulum. This interaction site has been titled mitochondria-associated ER membranes (MAM), and several studies have also shown that many cellular dysfunctions take place when ER-mitochondria contacts are perturbed in neurodegenerative diseases. These findings suggest a common mechanism that should be investigated to understand the progression of neurodegeneration and find new targets to develop better treatments. In this project, we have investigated whether pathogenic tau has an impact on ER-mitochondria interactions, focusing on tethering proteins in MAM site vesicle-associated membrane protein-associated protein B (VAPB) and protein tyrosine phosphatase interacting protein 51 (PTPIP51). Different methods were used to look into VAPB-PTPIP51 binding with luciferase assay on HEK293 cells, colocalisation of VAPBPTPIP51 with immunocytochemistry analysis and Immunofluorescent microscopy imaging on SH-SY5Y cells, and VAPB-PTPIP51 protein expression with western blotting on HEK293 and SH-SY5Y cells. In all experiments, cells were transfected with empty vector for control, WT tau, P301L tau and R406W tau mutations. Our results showed an increased binding between VAPB-PTPIP51 in mutant cells, especially R406W tau condition. However, no change in colocalisation of VAPB-PTPIP51 has been detected in immunocytochemistry experiment. VAPB and PTPIP51 protein expressions in western blots demonstrated no change in the presence of tau mutations, which were consistent with the findings of previous studies on other disease inducing proteins. Even though these results do not show very solid evidence for tau-induced changes in ER-mitochondria interactions, with modulations in experimental methods, these results can be a step forward in investigating tau-induced changes in a common mechanism that is disrupted in many neurodegenerative diseases. Understanding the function and dysfunction of MAM tethering site might present a highly promising target for developing future therapeutic approaches in the treatment of both tauopathies and other related neurodegenerative diseases.

Benzer Tezler

  1. Monitoring the ATPase domain dynamics of dnak upon nucleotide binding by using ion mobility mass spectrometry

    Dnak ATPase domeninin nükleotid bağlanma dinamiklerinin iyon hareketlilik kütle spektrometresiyle incelenmesi

    BARAN DİNGİLOĞLU

    Yüksek Lisans

    İngilizce

    İngilizce

    2019

    Biyofizikİstanbul Teknik Üniversitesi

    Moleküler Biyoloji-Genetik ve Biyoteknoloji Ana Bilim Dalı

    DOÇ. DR. GİZEM DİNLER DOĞANAY

  2. Assessment of the impacts of hyperlipidemia on brain and modulation of perk pathway against hyperlipidemia-induced synaptic impairment on hippocampus

    Hiperlipideminin beyin üzerine etkilerinin ve perk yolağı modulasyonunun hipokampüste görülen hiperlipidemi kaynaklı sinaptik bozukluğa etkisinin araştırılması

    BİLGE AŞKIN

    Yüksek Lisans

    İngilizce

    İngilizce

    2019

    BiyolojiOrta Doğu Teknik Üniversitesi

    Moleküler Biyoloji ve Genetik Ana Bilim Dalı

    DOÇ. DR. TÜLİN YANIK

    PROF. DR. MICHELLE ADAMS

  3. Endometriyal endotel hücrelerinde in vivo BİP ekspresyonu ve BİP'in inflamatuar sitokinler TNF-alfa ve İnterlökin 1 (IL-1) beta tarafından in vitro düzenlenmesi

    In vivo BİP expression in human endometrial endothelial cells and in vitro modulation of BİP by the inflammatory cytokines TNF-alpha and Interleukin 1 (IL-1) beta

    NEHİR ŞERİFE OCAK

    Yüksek Lisans

    Türkçe

    Türkçe

    2011

    Histoloji ve EmbriyolojiDokuz Eylül Üniversitesi

    Histoloji ve Embriyoloji Ana Bilim Dalı

    DOÇ. DR. H. ALPER BAGRİYANİK

  4. X-box binding protein 1'in pro-opiomelanokortin sentezleyen nöronlarda leptin sensitivitesi üzerine etkisi

    The effect of x-box binding protein 1 on leptin sensitivity of pro-opiomelanocortin synthesizing neurons

    ŞAFAK MERT

    Doktora

    Türkçe

    Türkçe

    2013

    BiyoteknolojiAnkara Üniversitesi

    Temel Biyoteknoloji Ana Bilim Dalı

    DOÇ. DR. ERKAN YILMAZ

  5. The ubiquitin/proteasome system related role of Bag-1L in breast cancer

    Bag-1L'in ubikuitin/proteazom sisteminde rolünün meme kanserinde incelenmesi

    SEVİLAY ACAR

    Yüksek Lisans

    İngilizce

    İngilizce

    2018

    Biyolojiİstanbul Teknik Üniversitesi

    Moleküler Biyoloji-Genetik ve Biyoteknoloji Ana Bilim Dalı

    DOÇ. DR. GİZEM DİNLER DOĞANAY