True or false? Alzheimer’s disease is type 3 diabetes: Evidences from bench to bedside

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 99, P. 102383 - 102383

Published: June 30, 2024

Globally, Alzheimer's disease (AD) is the most widespread chronic neurodegenerative disorder, leading to cognitive impairment, such as aphasia and agnosia, well mental symptoms, like behavioral abnormalities, that place a heavy psychological financial burden on families of afflicted. Unfortunately, no particular medications exist treat AD, current treatments only impede its progression.The link between AD type 2 diabetes (T2D) has been increasingly revealed by research; danger developing both T2D rises exponentially with age, being especially prone AD. This propelled researchers investigate mechanism(s) underlying this connection. A critical review relationship insulin resistance, Aβ, oxidative stress, mitochondrial hypothesis, abnormal phosphorylation Tau protein, inflammatory response, high blood glucose levels, neurotransmitters signaling pathways, vascular issues in diabetes, similarities two diseases, presented review. Grasping essential mechanisms behind detrimental interaction may offer chances devise successful therapeutic strategies.

Language: Английский

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Comparative outcomes of systemic diseases in people with type 2 diabetes, or obesity alone treated with and without GLP-1 receptor agonists: a retrospective cohort study from the Global Collaborative Network

Journal of Endocrinological Investigation, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 20, 2024

Language: Английский

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Protection against stroke with glucagon-like peptide-1 receptor agonists: a comprehensive review of potential mechanisms

Cardiovascular Diabetology, Journal Year: 2022, Volume and Issue: 21(1)

Published: Nov. 15, 2022

Abstract Several randomized controlled trials have demonstrated the benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on ischemic stroke in patients with diabetes. In this review, we summarize and discuss potential mechanisms protection by GLP-1RAs. GLP-1RAs exert multiple anti-atherosclerotic effects contributing to prevention such as enhanced plaque stability, reduced vascular smooth muscle proliferation, increased nitric oxide, improved endothelial function. also lower risk reducing traditional factors including hyperglycemia, hypertension, dyslipidemia. Independently these peripheral actions, show direct cerebral animal models, reduction infarct volume, apoptosis, oxidative stress, neuroinflammation, excitotoxicity, blood–brain barrier permeability, neurogenesis, neuroplasticity, angiogenesis, brain perfusion. Despite encouraging findings, further research is still needed understand more thoroughly which may mediate specifically human diabetic brain.

Language: Английский

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Mild behavioral impairment domains are longitudinally associated with pTAU and metabolic biomarkers in dementia‐free older adults

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(7), P. 4692 - 4701

Published: June 14, 2024

Abstract BACKGROUND The mechanisms linking mild behavioral impairment (MBI) and Alzheimer's disease (AD) have been insufficiently explored, with conflicting results regarding tau protein few data on other metabolic markers. We aimed to evaluate the longitudinal association of MBI domains a spectrum plasma biomarkers. METHODS Our study is secondary analysis from NOLAN. biomarkers, including pTau181, was tested using adjusted linear mixed‐effects models. RESULTS sample comprised 359 participants (60% female, mean age: 78.3, standard deviation: 0.3 years). After 1 year, domain abnormal perception associated steeper increases in pTau181. Abnormal perception, decreased motivation, impulse dyscontrol were homocysteine or insulin dysregulation. DISCUSSION Apart our suggest that might also represent dysregulation, probably contributing dementia transition among older adults subjective cognitive decline impairment. Highlights Mild psychosis p. pTau could be pharmacological target treat agitation symptoms. linked dysregulation involving homocysteine.

Language: Английский

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Role of mitogen-activated protein kinase inhibitors in Alzheimer's disease: Rouge of brain kinases

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: 224, P. 111296 - 111296

Published: March 10, 2025

Alzheimer's disease (AD) is the chief cause of dementia and related mortality worldwide due to progressive accumulation amyloid peptide (Aβ) hyperphosphorylated tau protein. These neuropathological changes lead cognitive impairment memory dysfunction. Notably, most Food drug Administration (FDA) approved anti-AD medications such as tacrine donepezil are engaged with symptomatic relief but do not reverse underlying AD neuropathology. Therefore, searching for new advisable. It has been shown that inflammatory signaling pathways mitogen-activated protein kinases (MAPK) intricate Aβ neuropathology in AD. In addition, inhibition brain MAPK plays a critical role mitigating dysfunction early-onset Though, fundamental mechanisms beneficial effects inhibitors were fully explained. this review aims discuss potential molecular

Language: Английский

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Development of Dementia in Type 2 Diabetes Patients: Mechanisms of Insulin Resistance and Antidiabetic Drug Development

Cells, Journal Year: 2022, Volume and Issue: 11(23), P. 3767 - 3767

Published: Nov. 25, 2022

Dementia is reported to be common in those with type 2 diabetes mellitus. Type contributes molecular mechanisms and an underlying pathology dementia. Brain cells becoming resistant insulin leads elevated blood glucose levels, impaired synaptic plasticity, microglial overactivation, mitochondrial dysfunction, neuronal apoptosis, nutrient deprivation, TAU (Tubulin-Associated Unit) phosphorylation, cholinergic dysfunction. If has neuroprotective properties, resistance may interfere properties. Risk factors have a significant impact on the development of diseases, such as diabetes, obesity, stroke, other conditions. Analysis risk importance for association between dementia important because they impede clinical management early diagnosis. We discuss pathological physiological behind mellitus dementia, resistance, signaling, sporadic forms dementia; relationship receptor activation phosphorylation; mRNA expression downregulation related receptors; neural modulation due secretion homeostasis; apoptosis Addressing these will offer outcome-based insights into connection patients cognitive impairment. Furthermore, we explore role brain evidence anti-diabetic drugs prevention diabetes.

Language: Английский

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Emerging Evidence for the Use of Antidiabetic Drugs, Glucagon-like Peptide 1 Receptor Agonists, for the Treatment of Alzheimer’s Disease

touchREVIEWS in Endocrinology, Journal Year: 2023, Volume and Issue: 19(1), P. 16 - 16

Published: Jan. 1, 2023

From an epidemiological and pathophysiological point of view, Alzheimer’s disease (AD) type 2 diabetes (T2DM) should be considered 'sister' diseases. T2DM significantly increases the risk developing AD, mechanisms neuronal degeneration themselves worsen peripheral glucose metabolism in multiple ways. The links between two diseases, particularly cerebral insulin resistance, which causes degeneration, are so close that AD is sometimes referred to as 'type 3 diabetes'. Although latest news on therapeutic front for encouraging, no treatment has been shown halt progression permanently. At best, treatments slow down progression; at worst, they inactive, or cause worrying side effects, preventing their use a larger scale. Therefore, it appears logical optimizing metabolic milieu through preventive curative measures can also characterizes AD. Among different classes hypoglycaemic drugs, glucagon-like peptide 1 receptor agonists, widely used T2DM, were down, even prevent, degeneration. Data from animal, preclinical, clinical phase II, cohort large cardiovascular outcomes studies encouraging. Of course, randomized III studies, on-going, will essential verify this hypothesis. Thus, once, there hope slowing neurodegenerative processes associated with diabetes, focus review.

Language: Английский

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Dopamine in the Regulation of Glucose Homeostasis, Pathogenesis of Type 2 Diabetes, and Chronic Conditions of Impaired Dopamine Activity/Metabolism: Implication for Pathophysiological and Therapeutic Purposes

Biomedicines, Journal Year: 2023, Volume and Issue: 11(11), P. 2993 - 2993

Published: Nov. 7, 2023

Dopamine regulates several functions, such as voluntary movements, spatial memory, motivation, sleep, arousal, feeding, immune function, maternal behaviors, and lactation. Less clear is the role of dopamine in pathophysiology type 2 diabetes mellitus (T2D) chronic complications conditions frequently associated with it. This review summarizes recent evidence on regulating insular metabolism activity, traditional T2D, pathophysiological interconnection between T2D neurological psychiatric disorders characterized by impaired activity/metabolism, therapeutic implications. Reinforcing signaling especially patients dopamine-related disorders, Parkinson’s Huntington’s diseases, addictions, attention-deficit/hyperactivity disorder. On other hand, although specific trials are probably needed, certain medications approved for (e.g., metformin, pioglitazone, incretin-based therapy, gliflozins) may have a due to anti-inflammatory anti-oxidative effects, improvement insulin signaling, neuroinflammation, mitochondrial dysfunction, autophagy, apoptosis, restoration striatal synthesis, modulation reward hedonic eating. Last, targeting could potential diagnostic purposes diabetes-related complications, diabetic retinopathy.

Language: Английский

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Combination treatment of SGLT2i and GLP-1RA associated with improved cardiovascular outcomes in type 2 diabetes patients with acute coronary syndrome: A propensity score-matched cohort study

International Journal of Cardiology, Journal Year: 2025, Volume and Issue: unknown, P. 133229 - 133229

Published: April 1, 2025

Few studies have investigated the effect of combined use sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) on cardiovascular (CV) composite outcomes in type 2 diabetes (T2D) patients with acute coronary syndrome (ACS). We retrospectively collected data 1325 T2D treated SGLT2i for more than 3 months before ACS admission at Civil Aviation General Hospital. According to initiative GLP-1RA after admission, were divided into a combination group (SGLT2i GLP-1RA) or group. The primary CV defined as first occurrence major adverse events (MACE) 1-year, encompassing all cause death, non-fatal myocardial infarction stroke, revascularization heart failure readmission. Propensity score-matched (PSM) was used control confounding factors. After matching, 208 pairs finally included. Compared group, demonstrated 31.0 % reduced risk MACE (HR = 0.690, 95 %CI: 0.488-0.976), attributed primarily substantial 22.9 0.771, 0.599-0.992) reduction all-cause mortality 36.3 stroke 0.637, 0.413-0.982). Subgroup analyses indicated consistent benefits across different subgroups (P interaction values >0.05). associated significantly decreased driven by lowering risks nonfatal ACS, compared alone.

Language: Английский

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The therapeutic effects and mechanisms of glucagon-like peptide-1 receptor agonists in neurocognitive disorders

Therapeutic Advances in Neurological Disorders, Journal Year: 2025, Volume and Issue: 18

Published: Jan. 1, 2025

Chronic cerebral hypoperfusion (CCH) represents a key pathogenic contributor to neurocognitive disorders. It can lead multifaceted pathological alterations including neuroinflammation, neuronal apoptosis, blood–brain barrier disruption, synaptic plasticity deficits, and mitochondrial dysfunction. The glucagon-like peptide-1 receptor (GLP-1R), ubiquitously expressed across multiple organ systems, exerts neuroprotective effects by maintaining intracellular homeostasis mitigating damage triggered oxidative stress, inflammatory cascades, apoptotic signaling, ischemic insults. Furthermore, GLP-1R activity is modulated gut microbiota composition short-chain fatty acid abundance, implicating the gut–brain axis in its regulatory influence on neurological function. This review systematically examines pathophysiological mechanisms underlying CCH highlights therapeutic potential of activation. Specifically, GLP-1R-targeted interventions attenuate hypoperfusion-induced through pleiotropic pathways crosstalk, thereby offering novel perspectives for advancing both fundamental research clinical management

Language: Английский

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