Investigations into the effects of the alzheimer's risk gene bin1 on tau subcellular location and propagation
Başlık çevirisi mevcut değil.
- Tez No: 797854
- Danışmanlar: Belirtilmemiş.
- Tez Türü: Yüksek Lisans
- Konular: Nöroloji, Psikoloji, Neurology, Psychology
- Anahtar Kelimeler: Belirtilmemiş.
- Yıl: 2022
- Dil: İngilizce
- Üniversite: University of East London
- Enstitü: Yurtdışı Enstitü
- Ana Bilim Dalı: Belirtilmemiş.
- Bilim Dalı: Belirtilmemiş.
- Sayfa Sayısı: 59
Özet
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Özet (Çeviri)
Recent GWAS studies have identified BIN1 as one of 8 other genes that are associated to late-onset Alzheimer's disease (Kamboh et al., 2012). As this is a gene that has been identified fairly recently, there are gaps in literature as to the nature of the association of BIN1 to AD. Studies have identified tau related changes when BIN1 levels are altered (Chapuis et al., 2013). Hence, this experiment has set out to further investigate how altered levels of BIN1 may contribute to tau subcellular location and propagation. Cortical neurones were dissected from E18 mice pups. BIN1 shRNA and control shRNA was used as viruses in this knock-out study. To understand the effects of BIN1 knockdown on the level of intracellular tau, PSD-95, synaptophysin, phosphorylated and dephosphorylated tau, Western-blot analysis was conducted, to understand the effects of knockdown on colocalization of tau with PSD-95, MAP2, synaptophysin and active synapses, these cells were stained and imaged by microscopy and analysed using image software. Finally, a western blot was conducted to understand the effects of treatment and extracellular tau release on cells with knockdown, followed by an ELISA, which was normalised against the blots. Some highlights of this research was a reduction in the level of tau when BIN1 was knocked down, BIN1 knockdown did not effect tau phosphorylation and tau was localised more with PSD-95 in the absence of BIN1. Also, the experiments found that there was more extracellular tau when BIN1 was knocked down in the treated condition
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