Global ETD Search

41	Synthesis of Thiophene-Vinyl-Benzothiazole Based Ligand Analogues for Detection of Aβ and Tau Pathology in Alzheimer's Disease Johansson, Joel January 2024 (has links) As of today, Alzheimer’s disease is the leading cause of dementia among neurodegenerative disorders, affecting many millions of people worldwide. As the average life span of populations increase, more and more people succumb to the illness each year. Like other neurodegenerative disorders, Alzheimer’s disease can be attributed to the accumulation of protein aggregates in the brain. These amyloid-β peptides and tau proteins can presumably be detected in the brain many years before the onset of clinical symptoms. Development of fluorescent ligands, capable of binding to these neuropathological hallmarks and highlighting them, could serve as molecular diagnostic tools and facilitate an early diagnosis of the disease. The method could also be useful in studying disease progression and evaluating the effects of novel treatments. One such ligand is HS-259. The aim of this project was to synthetize different analogues of HS-259, and test their selectivity towards the aforementioned aggregates in brain tissue from an individual with Alzheimer’s disease. Staining of tissue samples with analogue solution enables visualization of aggregate sites through fluorescence imaging. In the end, five analogues were synthetized, albeit in relatively low overall yields. Synthetic methods included Suzuki-Miyara cross-couplings, Ullmann-type arylations and condensations. Liquid Chromatography-Mass Spectrometry (LC-MS) and Nuclear Magnetic Resonance (NMR) were used for analysis of the compounds. Two of the five analogues could be tested for staining of aggregates and assessed for photophysical characteristics, i.e. absorption- and emission spectra. One analogue stained both amyloid-β aggregates and some tau aggregates, whereas the other stained neither. Since only two analogues were tested and rendered inconsistent results, further studies are needed to assess the binding properties of HS-259 analogues in general. Alzheimer's disease neurodegenerative disorders protein aggregates molecular ligands amyloid-β Aβ amyloid-beta tau diagnosis HS-259 staining brain tissue Suzuki coupling Ullmann arylation condensation NMR nuclear magnetic resonance LC-MS liquid chromatography neuropathological hallmarks absorption spectra emission spectra synthesis plaques symptoms neuropathology thiophene-vinyl-benzothiazole TVBT ligand analogues N-arylation Knoevenagel preparative LC PBS phosphate buffered saline treatments AD mechanisms thiophene benzothiazolium fluorescence imaging bTVBT bi-thiophene-vinyl-benzothiazole detection Suzuki-Miyara Organic Chemistry Organisk kemi
42	Development and Validation of Novel Polymer-based DNA Delivery Systems for Effective and Affordable Non-viral Gene Therapies Zhang, Jun 23 May 2022 (has links) No description available. Animal Diseases Biochemistry Biology Biomedical Engineering Biomedical Research Cellular Biology Developmental Biology Engineering Environmental Health Health Health Sciences Immunology Materials Science Medicine Molecular Biology Molecules Nanoscience Nanotechnology Neurobiology Neurology Neurosciences Organic Chemistry Pharmaceuticals Pharmacy Sciences Polymer Chemistry Polymers Public Health Toxicology Therapy Virology gene therapy gene delivery DNA delivery polymer non-viral nonviral therapeutic polyethylenimine PEI in vitro in vivo C2C12 muscle muscular M17 neuro neural brain transfection cell penetrating peptide neurodegenerative Alzheimer Parkinson prion PrP N1 C1 amyloid-β Aβ Tau α-synuclein αSyn α-cleavage ADAM8 pscAAV

Search results

Synthesis of Thiophene-Vinyl-Benzothiazole Based Ligand Analogues for Detection of Aβ and Tau Pathology in Alzheimer's Disease

Development and Validation of Novel Polymer-based DNA Delivery Systems for Effective and Affordable Non-viral Gene Therapies