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Αντισυμπληρωματικά ολιγονουκλεοτίδια για την θεραπεία της εγκεφαλικής παθολογίας της πρωτεΐνης Tau στη νόσο Alzheimer

Year: 2026
Type: article
Abstract: Alzheimer's disease (AD) is the most common neurodegenerative disorder that affects more than 55 million people worldwide and, so far, there is no disease-modifying therapy. Because abnormalities in the Tau protein represent a central hallmark of AD pathology, therapies that can modulate Tau-related pathology have become an important focus of research. The current master’s thesis investigated the therapeutic potential of antisense oligonucleotides (ASOs) designed to reduce Tau expression, using an in vivo approach in a THY-Tau22 transgenic mouse model that develops progressive Tau pathology. Selected human Tau-targeting ASOs were administered bilaterally via intracerebroventricular injection into the mouse brain, and their effects on behavior, hippocampal proteomic profiles, and synaptic pathology were evaluated through a combination of in vivo and in vitro approaches. Firstly, behavioral analyses revealed that Tau22 mice displayed impairments in associative and recognition memory and treatment with Tau-targeting ASOs improved several of these deficits, suggesting a beneficial effect on cognitive function. Next, proteomic analysis of hippocampal synaptosomal fractions revealed extensive alterations associated with Tau pathology and showed that ASO treatment partially restored protein expression patterns toward a wild-type profile. Finally, in primary neuronal cultures, ASO-mediated Tau reduction attenuated amyloid-β-induced synaptic pathology, as evidenced by preservation of synaptic markers and reduced pathological Tau accumulation at synaptic sites. Taken together, the present study provides encouraging evidence that Tau-targeting ASOs represent a promising therapeutic strategy for Tau-related neurodegeneration.
Language: English
Open Access status: green
OpenAlex ID: W7204675531
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