Alzheimer’s Disease as Type 3 Diabetes: Common Pathophysiological Mechanisms between Alzheimer’s Disease and Type 2 Diabetes

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(5), P. 2687 - 2687

Published: Feb. 28, 2022

Globally, the incidence of type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) epidemics is increasing rapidly has huge financial emotional costs. The purpose current review article to discuss shared pathophysiological connections between AD T2DM. Research findings are presented underline vital role that insulin plays in brain’s neurotransmitters, homeostasis energy, as well memory capacity. this indicate existence a mechanistic interplay pathogenesis with T2DM and, especially, disrupted signaling. interlinked resistance, neuroinflammation, oxidative stress, advanced glycosylation end products (AGEs), mitochondrial dysfunction metabolic syndrome. Beta-amyloid, tau protein amylin can accumulate brains. Given patients not routinely evaluated terms their cognitive status, they rarely treated for impairment. Similarly, high levels or Studies suggesting caused by resistance brain also offer strong support hypothesis 3 diabetes.

Language: Английский

---

Lipopolysaccharide-Induced Model of Neuroinflammation: Mechanisms of Action, Research Application and Future Directions for Its Use

Molecules, Journal Year: 2022, Volume and Issue: 27(17), P. 5481 - 5481

Published: Aug. 26, 2022

Despite advances in antimicrobial and anti-inflammatory therapies, inflammation its consequences still remain a significant problem medicine. Acute inflammatory responses are responsible for directly life-threating conditions such as septic shock; on the other hand, chronic can cause degeneration of body tissues leading to severe impairment their function. Neuroinflammation is defined an response central nervous system involving microglia, astrocytes, cytokines including chemokines. It considered important neurodegerative diseases, Alzheimer's disease, Parkinson's disease amyotrophic lateral sclerosis. Lipopolysaccharide (LPS) strong immunogenic particle present outer membrane Gram-negative bacteria. major triggering factor cascade bacteria infection. The use LPS pro-inflammatory agent well-known model applied both vivo vitro studies. This review offers summary pathogenesis associated with exposure, especially field neuroinflammation. Moreover, we analyzed different models utilized area neuroscience. paper presents recent knowledge focused new insights experimental model.

Language: Английский

---

Glucagon-like peptide-1 (GLP-1) receptor agonists and neuroinflammation: Implications for neurodegenerative disease treatment

Pharmacological Research, Journal Year: 2022, Volume and Issue: 186, P. 106550 - 106550

Published: Nov. 11, 2022

Chronic, excessive neuroinflammation is a key feature of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's (PD). However, neuroinflammatory pathways have yet to be effectively targeted in clinical treatments for diseases. Interestingly, increased inflammation risk been associated with type 2 diabetes mellitus (T2DM) insulin resistance (IR), suggesting that mitigate T2DM pathology may successful treating well. Glucagon-like peptide-1 (GLP-1) an incretin hormone promotes healthy signaling, regulates blood sugar levels, suppresses appetite. Consequently, numerous GLP-1 receptor (GLP-1R) stimulating drugs developed approved by the US Food Drug Administration (FDA) related global regulatory authorities treatment T2DM. Furthermore, GLP-1R anti-inflammatory, neurotrophic, neuroprotective properties disorder preclinical models, hence hold promise repurposing In this review, we discuss pathways, intersections between neuroinflammation, brain IR, diseases, focus on AD PD. We additionally overview current FDA-approved agents development, including unimolecular single, dual, triple agonists, highlight those trials treatment. propose already-approved agonists safe, efficacious, cost-effective strategy ameliorating PD quelling neuroinflammation.

Language: Английский

---

Pathogenesis, Diagnostics, and Therapeutics for Alzheimer's Disease: Breaking the Memory Barrier

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 101, P. 102481 - 102481

Published: Sept. 3, 2024

Alzheimer's disease (AD) is the most common cause of dementia and accounts for 60-70 % all cases. It affects millions people worldwide. AD poses a substantial economic burden on societies healthcare systems. progressive neurodegenerative disorder characterized by cognitive decline, memory loss, impaired daily functioning. As prevalence continues to increase, understanding its pathogenesis, improving diagnostic methods, developing effective therapeutics have become paramount. This comprehensive review delves into intricate mechanisms underlying AD, explores current state techniques, examines emerging therapeutic strategies. By revealing complexities this aims contribute growing body knowledge surrounding devastating disease.

Language: Английский

---

Biomarker-guided decision making in clinical drug development for neurodegenerative disorders

Nature Reviews Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

Language: Английский

---

Cerebrovascular insulin receptors are defective in Alzheimer’s disease

Brain, Journal Year: 2022, Volume and Issue: 146(1), P. 75 - 90

Published: Aug. 27, 2022

Central response to insulin is suspected be defective in Alzheimer's disease. As most secreted the bloodstream by pancreas, its capacity regulate brain functions must, at least partly, mediated through cerebral vasculature. However, how interacts with blood-brain barrier and whether alterations of this interaction could contribute disease pathophysiology both remain poorly defined. Here, we show that human murine receptors (INSRs), particularly long isoform INSRα-B, are concentrated microvessels rather than parenchyma. Vascular concentrations INSRα-B were lower parietal cortex subjects diagnosed disease, positively correlating cognitive scores, leading a shift towards higher INSRα-A/B ratio, consistent cerebrovascular resistance brain. INSRα was inversely correlated amyloid-β plaques β-site APP cleaving enzyme 1, but insulin-degrading enzyme, neprilysin P-glycoprotein. Using intracarotid perfusion, found transport rate across remained very low (<0.03 µl/g·s) not inhibited an receptor antagonist. perfusion induced phosphorylation INSRβ restricted microvessels. Such activation vascular blunted 3xTg-AD mice, suggesting neuropathology induces level barrier. Overall, present data post-mortem brains animal model indicate defects localized strongly association β-amyloid pathology.

Language: Английский

---

State of the Science on Brain Insulin Resistance and Cognitive Decline Due to Alzheimer’s Disease

Aging and Disease, Journal Year: 2023, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2023

Type 2 diabetes mellitus (T2DM) is common and increasing in prevalence worldwide, with devastating public health consequences. While peripheral insulin resistance a key feature of most forms T2DM has been investigated for over century, research on brain (BIR) more recently developed, including the context non-diabetes states. Recent data support presence BIR aging brain, even states, found that may be Alzheimer’s disease (AD) contributes to cognitive impairment. Further, therapies used treat are now being AD treatment prevention, insulin. In this review, we offer definition BIR, present evidence AD; discuss expression, function, activation receptor (INSR) brain; how could develop; tools study BIR; correlates current hallmarks; regional/cellular involvement BIR. We close discussion resilience both AD, can improved better understand future avenues research. Overall, review position paper highlights as plausible therapeutic target prevention decline dementia due AD.

Language: Английский

---

Diabetes: Risk factor and translational therapeutic implications for Alzheimer's disease

European Journal of Neuroscience, Journal Year: 2022, Volume and Issue: 56(9), P. 5727 - 5757

Published: Feb. 7, 2022

Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) commonly co-occur. T2DM increases the risk for AD by approximately twofold. Animal models provide one means of interrogating relationship to investigating brain insulin resistance in pathophysiology AD. show that persistent hyperglycaemia results chronic low-grade inflammation may contribute development neuroinflammation accelerate pathobiology Epidemiological studies suggest patients with who received treatment specific anti-diabetic agents have a decreased occurrence all-cause dementia. Agents such as metformin ameliorate other important systemic effects lower Glucagon-like peptide 1 (GLP-1) agonists been associated T2DM. Both non-insulin treatments evaluated clinical trials. In most cases, included trials features but do not Many were conducted prior use diagnostic biomarkers Trials had wide range durations population sizes. used treat cross blood barrier, are posited occur via lowering peripheral reduction central inflammation. Clinical ongoing will insight into therapeutic utility these agents.

Language: Английский

---

Dapagliflozin Ameliorates Cognitive Impairment in Aluminum-Chloride-Induced Alzheimer’s Disease via Modulation of AMPK/mTOR, Oxidative Stress and Glucose Metabolism

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(5), P. 753 - 753

Published: May 16, 2023

Alzheimer's disease (AD) is a progressive neurological illness characterized by memory loss and cognitive deterioration. Dapagliflozin was suggested to attenuate the impairment associated with AD; however, its mechanisms were not fully elucidated. This study aims examine possible of neuroprotective effects dapagliflozin against aluminum chloride (AlCl3)-induced AD. Rats distributed into four groups: group 1 received saline, 2 AlCl3 (70 mg/kg) daily for 9 weeks, groups 3 4 administered 5 weeks. (1 (5 then given another Two behavioral experiments performed: Morris Water Maze (MWM) Y-maze spontaneous alternation (Y-maze) task. Histopathological alterations in brain, as well changes acetylcholinesterase (AChE) amyloid β (Aβ) peptide activities oxidative stress (OS) markers, all evaluated. A western blot analysis used detection phosphorylated 5' AMP-activated protein kinase (p-AMPK), mammalian target Rapamycin (p-mTOR) heme oxygenase-1 (HO-1). Tissue samples collected isolation glucose transporters (GLUTs) glycolytic enzymes using PCR analysis, brain levels also measured. The current data demonstrate that represents approach combat AlCl3-induced AD rats through inhibiting stress, enhancing metabolism activating AMPK signaling.

Language: Английский

---

Mitochondria and Oxidative Stress as a Link between Alzheimer’s Disease and Diabetes Mellitus

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14450 - 14450

Published: Sept. 22, 2023

This review is devoted to the problems of common features linking metabolic disorders and type 2 diabetes with development Alzheimer’s disease. The pathogenesis disease closely intersects mechanisms development, an important risk factor for both pathologies aging. Common pathological include factors in oxidative stress, neuroinflammation, insulin resistance, amyloidosis, as well impaired mitochondrial dysfunctions increasing cell death. currently available drugs treatment have limited therapeutic efficacy. It note that used treat disease, particular acetylcholinesterase inhibitors, show a positive potential diabetes, while can also prevent number characteristic A promising direction search strategy may be creation complex multi-target neuroprotective affect specific targets

Language: Английский

---