These data indicate that ABCA1-induced lipidation of ApoE is necessary for the ability of bexarotene to clear hippocampal soluble Aβ and ameliorate cognitive deficits.
Bexarotene, an agonist of retinoid X receptor alpha (RXRα), has been shown to increase the expression of apoE, ABCA1, and ABCG1 by activating RXR/LXR and RXR/PPAR heterodimers, resulting in amyloid β (Aβ)-protein clearance in the brain of an Alzheimer's disease (AD) mouse model and reversal of mouse cognitive deficits.
ACAT1 gene ablation (A1-) in triple transgenic (i.e., 3XTg-AD) mice leads to more than 60% reduction in full-length human APPswe as well as its proteolytic fragments, and ameliorates cognitive deficits.
In conclusion, dimenazine-induced stimulation of ACE2/Ang(1-7)/Mas axis subdues cognitive deficits in AD most probably through activation of PI3K/Akt pathway.
Cognitive deficits (passive avoidance and spatial memory), oxidative stress parameters, acetylcholinesterase (AChE) activity, and percentage of cell loss were evaluated in the hippocampus.
These studies determined whether the acetylcholinesterase inhibitors, donepezil and galantamine, both of which are approved for the treatment of cognitive deficits in Alzheimer's disease, can prevent or reverse spatial memory deficits in mice induced by cyclophosphamide and doxorubicin, cytotoxic agents commonly used to treat breast cancer.
Enhancement of cholinergic functions in the brain via acetylcholinesterase inhibition is one of the main therapeutic strategies to improve symptoms associated with Alzheimer's or related cognitive deficits.
In addition, sleep deprivation successfully induces cognitive deficits in adult mouse lemurs, and the effectiveness of approved cognitive enhancers such as acetylcholinesterase inhibitors or N-methyl-D-aspartate antagonists is demonstrated in sleep-deprived animals.
Combining sub-effective doses of TAK-071, but not T-662, with an acetylcholinesterase inhibitor, significantly ameliorated scopolamine-induced cognitive deficits in rats.
S-allyl cysteine ameliorates cognitive deficits in streptozotocin-diabetic rats via suppression of oxidative stress, inflammation, and acetylcholinesterase.
Cognitive deficits (short-term memory and spatial memory), oxidative stress parameters, and acetylcholinesterase (AChE) and Na<sup>+</sup>-K<sup>+</sup>-ATPase activity in the cerebral cortex and hippocampus were evaluated.
Importantly, the demonstration that acetylcholinesterase inhibitors, which result in higher synaptic levels of acetylcholine, can reduce the cognitive deficits of schizophrenia suggested that under-stimulation of cholinoceptors could be associated with the cognitive deficits associated with this disorder.
As part of the G-protein coupled receptor (GPCR) family, metabotropic glutamate (mGlu) receptors play an important role as drug targets of cognitive diseases.
These results suggest the hypothesis that defective actin/membrane modulation in IRSp53-deficient dendritic spines may lead to social and cognitive deficits through NMDA receptor dysfunction.
F-actin decrease correlated inversely with increasing AD pathology (Braak score, Aβ load, and tangle density) and directly with performance in episodic and working memory tasks, suggesting its role in human disease pathogenesis and progression.<b>SIGNIFICANCE STATEMENT</b> Synaptic dysfunction underlies cognitive deficits in Alzheimer's disease (AD).
Increased Training Intensity Induces Proper Membrane Localization of Actin Remodeling Proteins in the Hippocampus Preventing Cognitive Deficits: Implications for Fragile X Syndrome.