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- W4200501792 abstract "Amyloid-induced neurodegeneration plays a central role in Alzheimer’s disease (AD) pathogenesis. Here, we show that telomerase reverse transcriptase (TERT) haploinsufficiency decreases brain-derived neurotrophic factor and increases amyloid-β precursor in the murine brain. Moreover, before disease onset, the TERT locus sustains accumulation of repressive epigenetic marks in murine and human AD neurons, implicating TERT repression in amyloid-induced neurodegeneration. To test the impact of sustained TERT expression on AD pathobiology, AD mouse models were engineered to maintain physiological levels of TERT in adult neurons, resulting in reduced amyloid-β accumulation, improved spine morphology and preserved cognitive function. Mechanistically, integrated profiling revealed that TERT interacts with β-catenin and RNA polymerase II at gene promoters and upregulates the gene networks governing synaptic signaling and learning processes. These TERT-directed transcriptional activities do not require its catalytic activity nor telomerase RNA. These findings provide genetic proof of concept for somatic TERT gene activation therapy in attenuating AD progression including cognitive decline. The authors link neuronal expression of telomerase reverse transcriptase to amyloid pathology and cognitive dysfunction in preclinical models of Alzheimer’s disease." @default.
- W4200501792 created "2021-12-31" @default.
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- W4200501792 date "2021-12-20" @default.
- W4200501792 modified "2023-10-18" @default.
- W4200501792 title "Telomerase reverse transcriptase preserves neuron survival and cognition in Alzheimer’s disease models" @default.
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