Publications by authors named "A G Tetlow"

Introduction: It is unclear how early neuronal deficits occur in tauopathies, if these are associated with changes in neuronal network activity, and if they can be alleviated with therapies.

Methods: To address this, we performed in vivo two-photon Ca imaging in tauopathy mice at 6 versus 12 months, compared to controls, and treated the younger animals with a tau antibody.

Results: Neuronal function was impaired at 6 months but did not deteriorate further at 12 months, presumably because cortical tau burden was comparable at these ages.

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Article Synopsis
  • Synucleinopathies are neurodegenerative diseases marked by the buildup of α-synuclein in the brain, causing various motor and psychological symptoms, with no current cures available.
  • A new approach using a single-domain antibody (sdAb)-based protein degrader has been developed to promote the breakdown of α-synuclein by targeting both α-syn and a receptor that aids in its degradation.
  • This study shows that the sdAb effectively enhances the removal of α-synuclein in laboratory and mouse models, suggesting it could be a promising therapy for synucleinopathies and could lead to improved brain access compared to traditional antibodies.
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Unlabelled: We previously reported altered neuronal Ca dynamics in the motor cortex of 12-month-old JNPL3 tauopathy mice during quiet wakefulness or forced running, with a tau antibody treatment significantly restoring the neuronal Ca activity profile and decreasing pathological tau in these mice . Whether neuronal functional deficits occur at an early stage of tauopathy and if tau antibody treatment is effective in younger tauopathy mice needed further investigation. In addition, neuronal network activity and neuronal firing patterns have not been well studied in behaving tauopathy models.

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Synucleinopathies are a group of neurodegenerative diseases characterized by the accumulation of α-synuclein (α-syn) in the brain, leading to motor and neuropsychiatric symptoms. Currently, there are no known cures for synucleinopathies, and treatments mainly focus on symptom management. In this study, we developed a single-domain antibody (sdAb)-based protein degrader with features designed to enhance proteasomal degradation of α-syn.

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Background: Cancer is a dynamic process and thus requires highly informative and reliable biomarkers to help guide patient care. Liquid-based biopsies have emerged as a clinical tool for tracking cancer dynamics. Extracellular vesicles (EVs), lipid bilayer delimited particles secreted by cells, are a new class of liquid-based biomarkers.

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