Akt activation ameliorates deficits in hippocampal-dependent memory and activity-dependent synaptic protein synthesis in an Alzheimer’s disease mouse model

Kommaddi, Reddy Peera; Gowaikar, Ruturaj; P A, Haseena; Diwakar, Latha; Singh, Kunal; Mondal, Amrita

doi:10.1016/j.jbc.2023.105619

Cited by 4 publications

(1 citation statement)

References 104 publications

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“…Furthermore, it was observed that estrogens augmented the uptake of accumulated Aβ by microglia in the human cortex (Testo et al, 2024;Yamada et al, 2024). The potential of estrogens to reduce plaque load in animal models has been observed through their actions (Kommaddi et al, 2024). The findings suggest that estradiol has the potential to reduce Aβ levels in HEK293 cells, enhance soluble APP in ZR-75-1 human carcinoma cells and promote APP trafficking in the trans-Golgi network in vesicles, leading to a decrease in Aβ synthesis (Guarnieri et al, 2024).…”

Section: Modulation Of Estrogen Signallingmentioning

confidence: 99%

Estrogen signalling and Alzheimer's disease: Decoding molecular mechanisms for therapeutic breakthrough

Rishabh,

Rohilla,

Bansal

et al. 2024

Eur J of Neuroscience

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In females, Alzheimer's disease (AD) incidences increases as compared to males due to estrogen deficiency after menopause. Estrogen therapy is the mainstay therapy for menopause and associated complications. Estrogen, a hormone with multifaceted physiological functions, has been implicated in AD pathophysiology. Estrogen plays a crucial role in amyloid precursor protein (APP) processing and overall neuronal health by regulating various factors such as brain‐derived neurotrophic factor (BDNF), intracellular calcium signalling, death domain‐associated protein (Daxx) translocation, glutamatergic excitotoxicity, Voltage‐Dependent Anion Channel, Insulin‐Like Growth Factor 1 Receptor, estrogen‐metabolising enzymes and apolipoprotein E (ApoE) protein polymorphisms. All these factors impact the physiology of postmenopausal women. Estrogen replacement therapies play an important treatment strategy to prevent AD after menopause. However, use of these therapies may lead to increased risks of breast cancer, venous thromboembolism and cardiovascular disease. Various therapeutic approaches have been used to mitigate the effects of estrogen on AD. These include hormone replacement therapy, Selective Estrogen Receptor Modulators (SERMs), Estrogen Receptor Beta (ERβ)‐Selective Agonists, Transdermal Estrogen Delivery, Localised Estrogen Delivery, Combination Therapies, Estrogen Metabolism Modulation and Alternative Estrogenic Compounds like genistein from soy, a notable phytoestrogen from plant sources. However, mechanism via which these approaches modulate AD in postmenopausal women has not been explained earlier thoroughly. Present review will enlighten all the molecular mechanisms of estrogen and estrogen replacement therapies in AD. Along‐with this, the association between estrogen, estrogen‐metabolising enzymes and ApoE protein polymorphisms will also be discussed in postmenopausal AD.

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Section: Modulation Of Estrogen Signallingmentioning

confidence: 99%

Estrogen signalling and Alzheimer's disease: Decoding molecular mechanisms for therapeutic breakthrough

Rishabh,

Rohilla,

Bansal

et al. 2024

Eur J of Neuroscience

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Nanocurcumin prevents memory impairment, hippocampal apoptosis, Akt and CaMKII-α signaling disruption in the central STZ model of Alzheimer’s disease in rat

Moosavi,

soukhaklari,

Bagheri-Mohammadi

et al. 2024

Behavioural Brain Research

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Hippocampal Leptin Resistance and Cognitive Decline: Mechanisms, Therapeutic Strategies and Clinical Implications

Valladolid-Acebes

2024

Biomedicines

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Background: Leptin, an adipokine essential for regulating energy balance, exerts important effects on brain function, notably within the hippocampus, a region integral to learning and memory. Leptin resistance, characterized by diminished responsiveness to elevated leptin levels, disrupts hippocampal function and exacerbates both obesity and cognitive impairments. Scope: This review critically examines how leptin resistance impairs hippocampal synaptic plasticity processes, specifically affecting long-term potentiation (LTP) and long-term depression (LTD), which are crucial for cognitive performance. Findings: Recent research highlights that leptin resistance disrupts N-methyl-D-aspartate (NMDA) receptor dynamics and hippocampal structure, leading to deficits in spatial learning and memory. Additionally, high-fat diets (HFDs), which contribute to leptin resistance, further deteriorate hippocampal function. Potential therapeutic strategies, including leptin sensitizers, show promise in mitigating brain disorders associated with leptin resistance. Complementary interventions such as caloric restriction and physical exercise also enhance leptin sensitivity and offer potential benefits to alleviating cognitive impairments. Aims of the review: This review synthesizes recent findings on the molecular pathways underlying leptin resistance and its impact on synaptic transmission and plasticity in the hippocampus. By identifying potential therapeutic targets, this work aims to provide an integrated approach for addressing cognitive deficits in obesity, ultimately improving the quality of life for affected individuals.

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Akt activation ameliorates deficits in hippocampal-dependent memory and activity-dependent synaptic protein synthesis in an Alzheimer’s disease mouse model

Cited by 4 publications

References 104 publications

Estrogen signalling and Alzheimer's disease: Decoding molecular mechanisms for therapeutic breakthrough

Estrogen signalling and Alzheimer's disease: Decoding molecular mechanisms for therapeutic breakthrough

Nanocurcumin prevents memory impairment, hippocampal apoptosis, Akt and CaMKII-α signaling disruption in the central STZ model of Alzheimer’s disease in rat

Hippocampal Leptin Resistance and Cognitive Decline: Mechanisms, Therapeutic Strategies and Clinical Implications

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