Neuroprotective Effect of SGLT2 Inhibitors

Molecules, Год журнала: 2021, Номер 26(23), С. 7213 - 7213

Опубликована: Ноя. 28, 2021

Patients with diabetes are at higher risk of cardiovascular diseases and cognitive impairment. SGLT2 inhibitors (Empagliflozin, Canagliflozin, Dapagliflozin, Ertugliflozin, Sotagliflozin) newer hypoglycemic agents many pleiotropic effects. In this review, we discuss their neuroprotective potential. (SGLT2i) lipid-soluble reach the brain/serum ratio from 0.3 to 0.5. SGLT receptors present in central nervous system (CNS). Flozins not fully SGLT2-selective have an affinity for SGLT1 receptor, which is associated protection against ischemia/reperfusion brain damage. SGLT2i show anti-inflammatory anti-atherosclerotic effect, including reduction proinflammatory cytokines, M2 macrophage polarization, JAK2/STAT1 NLRP3 inflammasome inhibition, as well cIMT regression. They also mitigate oxidative stress. improve endothelial function, prevent remodeling exert a protective effect on neurovascular unit, blood-brain barrier, pericytes, astrocytes, microglia, oligodendrocytes. able inhibit AChE, contributes improvement. Empagliflozin significantly increases level cerebral BDNF, modulates neurotransmission ensures growth, survival, plasticity neurons. Moreover, they may be restore circadian rhythm mTOR activation, quite novel finding field research metabolic great potential protect atherosclerosis impairment patients type 2 mellitus.

Язык: Английский

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Astrocyte energy and neurotransmitter metabolism in Alzheimer’s disease: Integration of the glutamate/GABA-glutamine cycle

Progress in Neurobiology, Год журнала: 2022, Номер 217, С. 102331 - 102331

Опубликована: Июль 21, 2022

Язык: Английский

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Energy matters: presynaptic metabolism and the maintenance of synaptic transmission

Nature reviews. Neuroscience, Год журнала: 2021, Номер 23(1), С. 4 - 22

Опубликована: Ноя. 15, 2021

Язык: Английский

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Current Strategies to Enhance Delivery of Drugs across the Blood–Brain Barrier

Pharmaceutics, Год журнала: 2022, Номер 14(5), С. 987 - 987

Опубликована: Май 4, 2022

The blood–brain barrier (BBB) has shown to be a significant obstacle brain medication delivery. BBB in healthy is diffusion that prevents most substances from passing the blood brain; only tiny molecules can pass across BBB. disturbed specific pathological illnesses such as stroke, diabetes, seizures, multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease. goal of this study offer general overview current delivery techniques associated topics last five years. It anticipated review will stimulate readers look into new ways deliver medications brain. Following an introduction construction function both conditions, revisits certain contested questions, whether nanoparticles may cross on their own if are selectively delivered by deliberately targeted nanoparticles. Current non-nanoparticle options also discussed, including drug via permeable under circumstances use non-invasive approaches improve absorption.

Язык: Английский

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Intranasal Insulin for Alzheimer’s Disease

CNS Drugs, Год журнала: 2021, Номер 35(1), С. 21 - 37

Опубликована: Янв. 1, 2021

Brain insulin signaling contributes to memory function and might be a viable target in the prevention treatment of impairments including Alzheimer's disease. This short narrative review explores potential central nervous system (CNS) administration via intranasal pathway improve performance health disease, with focus on most recent results. Proof-of-concept studies (pilot) clinical trials individuals mild cognitive impairment or disease indicate that acute prolonged enhances performance, suggest brain resistance is pathophysiological factor without concomitant metabolic dysfunction. Intranasally administered assumed trigger improvements synaptic plasticity regional glucose uptake as well alleviations neuropathology; additional contributions changes hypothalamus-pituitary-adrenocortical axis activity sleep-related mechanisms are discussed. While delivery has been conclusively demonstrated effective safe, outcomes large-scale underline need for further investigations, which also yield new insights into sex differences response contribute optimization devices grasp full

Язык: Английский

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Cognitive impairment and type 2 diabetes mellitus: Focus of SGLT2 inhibitors treatment

Pharmacological Research, Год журнала: 2022, Номер 176, С. 106062 - 106062

Опубликована: Янв. 10, 2022

Gliflozins are a novel class of oral anti-diabetic drugs, acting as inhibitors sodium-glucose co-transporters (SGLTs) through the proximal convoluted tubules (PCT) and intestinal epithelium. The 2 (SGLT2) mainly expressed in S1 S2 segments tubule kidneys. Clinical guidelines recommend their use especially Type Diabetes mellitus (T2DM) patients with vascular complications and/or heart failure highlighting importance co-transporter (SGLT2i) pleiotropic effects. Interestingly, cognitive decline is widely recognized complication T2DM and, addition, to clarify its pathophysiology, there an urgent need understand how if diabetes therapies can control diabetes-related dysfunction. At time, although SGLT2 proteins present Central Nervous System (CNS), SGLT2i effects on impairments remain partly unknown. In pre-clinical studies, ameliorates dysfunction obese mice, reducing oxidative stress, neuroinflammation improving neuronal plasticity mitochondrial brain pathway. could bring back mTOR physiological state activation, stopping neurodegenerative diseases' onset or progression. Instead, clinical studies T2DM-related treated by much more limited. For these reasons, further needed better elucidate therapy affect decline. this scenario, review aims summarize knowledge role stimulate new trials.

Язык: Английский

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Blood–Brain Barrier Breakdown in Alzheimer’s Disease: Mechanisms and Targeted Strategies

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(22), С. 16288 - 16288

Опубликована: Ноя. 14, 2023

The blood-brain barrier (BBB) is a unique and selective feature of the central nervous system's vasculature. BBB dysfunction has been observed as an early sign Alzheimer's Disease (AD) before onset dementia or neurodegeneration. intricate relationship between pathogenesis AD, especially in context neurovascular coupling overlap pathophysiology neurodegenerative cerebrovascular diseases, underscores urgency to understand BBB's role more deeply. Preserving restoring function emerges potentially promising strategy for mitigating progression severity AD. Molecular genetic changes, such isoform ε4 apolipoprotein E (ApoEε4), significant risk factor promoter dysfunction, have shown mediate disruption. Additionally, receptors transporters like low-density lipoprotein receptor-related protein 1 (LRP1), P-glycoprotein (P-gp), receptor advanced glycation end products (RAGEs) implicated AD's pathogenesis. In this comprehensive review, we endeavor shed light on pathogenic therapeutic connections AD BBB. We also delve into latest developments pioneering strategies targeting interventions, addressing its potential carrier. By providing integrative perspective, anticipate paving way future research treatments focused exploiting therapy.

Язык: Английский

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Semaglutide ameliorates cognition and glucose metabolism dysfunction in the 3xTg mouse model of Alzheimer's disease via the GLP-1R/SIRT1/GLUT4 pathway

Neuropharmacology, Год журнала: 2023, Номер 240, С. 109716 - 109716

Опубликована: Сен. 18, 2023

Язык: Английский

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Astrocyte metabolism and signaling pathways in the CNS

Frontiers in Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Сен. 4, 2023

Astrocytes comprise half of the cells in central nervous system and play a critical role maintaining metabolic homeostasis. Metabolic dysfunction astrocytes has been indicated as primary cause neurological diseases, such depression, Alzheimer’s disease, epilepsy. Although functionalities are well known, their relationship to disorders is poorly understood. The ways which regulate metabolism glucose, amino acids, lipids have all implicated diseases. Metabolism also exhibited significant influence on neuron functionality brain’s neuro-network. In this review, we focused processes present astrocytes, most notably glucose pathway, fatty acid amino-acid pathway. For metabolism, glycolysis pentose-phosphate oxidative phosphorylation followed oxidation, ketone body sphingolipid metabolism. summarized neurotransmitter serine kynurenine pathways. This review will provide an overview functional changes astrocyte overall perspective current treatment therapy for disorders.

Язык: Английский

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Energy metabolism in health and diseases

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Фев. 18, 2025

Язык: Английский

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