Primate-specific 82-kDa choline acetyltransferase attenuates progression of Alzheimer's disease-like pathology in the APP knock-in mouse model.

Alzheimer's disease (AD) is characterized by amyloidosis, neuroinflammation, cholinergic dysfunction and cognitive impairment. In AD, the cholinergic neuronal marker choline acetyltransferase (ChAT) is reduced and the primate-specific nuclear isoform, 82-kDa ChAT, is mislocalized to cytoplasm. Cell-based studies suggest a role for 82-kDa ChAT in regulating expression of AD-related genes with potential reductions in β-amyloid (Aβ) levels.

Navigating the Landscape of Translational Geroscience in Canada: A Comprehensive Evaluation of Current Progress and Future Directions.

The inaugural Canadian Conferences on Translational Geroscience were held as 2 complementary sessions in October and November 2023. The conferences explored the profound interplay between the biology of aging, social determinants of health, the potential societal impact of geroscience, and the maintenance of health in aging individuals. Although topics such as cellular senescence, molecular and genetic determinants of aging, and prevention of chronic disease were addressed, the conferences went on to emphasize practical applications for enhancing older people's quality of life.

Attenuation of Oxidative Stress in HEK 293 Cells by the TCM Constituents Schisanhenol, Baicalein, Resveratrol or Crocetin and Two Defined Mixtures.

Purpose: Our working hypothesis is that single bioactive phytochemicals with antioxidant properties that are important constituents of Traditional Chinese Medicine (TCM) and their defined mixtures have potential as chemoprotective agents for chronic conditions characterized by oxidative and nitrosative stress, including Alzheimer's. Here we evaluate the ability of baicalein, crocetin, trans-resveratrol or schisanhenol and two defined mixtures of these TCM phytochemicals to attenuate the toxicity resulting from exposure to cell permeant t-butyl hydroperoxide (tBPH) in wild-type and bioengineered (to express choline acetyltransferase) HEK 293 cells.

Methods: Endpoints of tBHP-initiated oxidative and nitrosative stress in both types of HEK 293 cells and its attenuation by TCM constituents and mixtures included cytotoxicity (LDH release); depletion of intracellular glutathione (GSH); formation of S-glutathionylated proteins; oxidative changes to the disulfide proteome; and real-time changes in intracellular redox status.

Differential regulation of the high-affinity choline transporter by wild-type and Swedish mutant amyloid precursor protein.

The high-affinity choline transporter (CHT) is responsible for choline uptake into cholinergic neurons, with this being the rate-limiting step for acetylcholine production. Altering CHT protein disposition directly impacts choline uptake activity and cholinergic neurotransmission. Amyloid precursor protein (APP) interacts with CHT proteins and increases their endocytosis from the cell surface.

Regulation of the high-affinity choline transporter activity and trafficking by its association with cholesterol-rich lipid rafts.

The sodium-coupled, hemicholinium-3-sensitive, high-affinity choline transporter (CHT) is responsible for transport of choline into cholinergic nerve terminals from the synaptic cleft following acetylcholine release and hydrolysis. In this study, we address regulation of CHT function by plasma membrane cholesterol. We show for the first time that CHT is concentrated in cholesterol-rich lipid rafts in both SH-SY5Y cells and nerve terminals from mouse forebrain.