Astrocytic and microglial cells as the modulators of neuroinflammation in Alzheimer’s disease

Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)

Published: Aug. 17, 2022

Abstract Neuroinflammation is instigated by the misfiring of immune cells in central nervous system (CNS) involving microglia and astrocytes as key cell-types. a consequence CNS injury, infection, toxicity, or autoimmunity. It favorable well detrimental process for neurodevelopment associated processes. Transient activation inflammatory response release cytokines growth factors positively affects development post-injury tissue. However, chronic uncontrolled responses may lead to various neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's (PD), amyotrophic lateral sclerosis, multiple sclerosis. These diseases have variable clinical pathological features, but are underlaid aggregation misfolded proteins with cytotoxic effect. Notably, abnormal glial could mediate neuroinflammation, leading condition. Microglia, type cell, resident form forefront defense system. Dysfunctional astrocyte, different kind cell homeostatic function, impairs protein aggregate (amyloid-beta plaque) clearance AD. Studies shown that undergo alterations their genetic profile, cellular molecular responses, thus promote dysfunctional cross-talk Hence, targeting astrocytes-driven pathways resolve particular layers neuroinflammation set reliable therapeutic intervention AD progression.

Language: Английский

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Microglia Phenotypes in Aging and Neurodegenerative Diseases

Cells, Journal Year: 2022, Volume and Issue: 11(13), P. 2091 - 2091

Published: June 30, 2022

Neuroinflammation is a hallmark of many neurodegenerative diseases (NDs) and plays fundamental role in mediating the onset progression disease. Microglia, which function as first-line immune guardians central nervous system (CNS), are drivers neuroinflammation. Numerous human postmortem studies vivo imaging analyses have shown chronically activated microglia patients with various acute chronic neuropathological diseases. While microglial activation common feature NDs, exact pathological states complex often contradictory. However, there consensus that play biphasic conditions, detrimental protective phenotypes, overall response different phenotypes depends on nature duration inflammatory insult, well stage disease development. This review provides comprehensive overview current research responses health, aging, special emphasis heterogeneous phenotypic such hemorrhagic stroke (HS), Alzheimer's (AD), Parkinson's (PD). The primary focus translational preclinical animal models bulk/single-cell transcriptome samples. Additionally, this covers key receptors signaling pathways potential therapeutic targets to regulate during aging NDs. age-, sex-, species-specific differences will be briefly reviewed.

Language: Английский

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Protective Effects of Pioglitazone on Cognitive Impairment and the Underlying Mechanisms: A Review of Literature

Drug Design Development and Therapy, Journal Year: 2022, Volume and Issue: Volume 16, P. 2919 - 2931

Published: Aug. 1, 2022

Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, is known to have anti-inflammatory and anti-oxidant effects on the brain, its clinical potential in treatment of cognitive impairment diseases such as Alzheimer's disease (AD) Parkinson (PD) currently being explored. This review focused reported beneficial pioglitazone dysfunction summarized associated mechanisms with pioglitazone-induced improvement dysfunction. Our relevant literature indicated that there conclusive evidence effect improving via agonistic PPAR-γ. Further, several action been reported, these include enhanced NF-kB p38 activity; regulation pro-inflammatory cytokines IL-1, IL-6, TNF-α; inhibition Aβ production; alterations levels mitochondrial proteins mitoNEET; protein kinases CDK5 JNK; ROS MDA antioxidant TRX1 PON2; increased expression thyroid hormone receptors. Despite promising findings, also cardiovascular risks, weight gain edema, which subsequently increase risk mortality. it has documented may be unable cross blood-brain barrier when administered certain forms, can cause cell death at high concentrations. Therefore, further research required explore acute chronic memory function order determine applicability disorders. Nonetheless, current does demonstrate promotes PPAR receptors ameliorating inflammation, oxidative stress, amyloidogenesis, hypothyroidism, enhancing neurogenesis, synaptic plasticity, function. warrant investigation establish disorders, PD AD, neuronal conditions diabetes.

Language: Английский

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Intranasal Drug Administration in Alzheimer-Type Dementia: Towards Clinical Applications

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(5), P. 1399 - 1399

Published: May 3, 2023

Alzheimer-type dementia (ATD) treatments face limitations in crossing the blood–brain barrier and systemic adverse effects. Intranasal administration offers a direct route to brain via nasal cavity’s olfactory trigeminal pathways. However, physiology can hinder drug absorption limit bioavailability. Therefore, physicochemical characteristics of formulations must be optimized by means technological strategies. Among strategies that have been explored, lipid-based nanosystems, particularly nanostructured lipid carriers, are promising preclinical investigations with minimal toxicity therapeutic efficacy due their ability overcome challenges associated other nanocarriers. We review studies carriers for intranasal treatment ATD. Currently, no drugs ATD marketing approval, only three candidates, insulin, rivastigmine APH-1105, being clinically investigated. Further different candidates will eventually confirm potential

Language: Английский

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Alzheimer’s Disease as Type 3 Diabetes: Understanding the Link and Implications

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 11955 - 11955

Published: Nov. 7, 2024

Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are two prevalent conditions that present considerable public health issue in aging populations worldwide. Recent research has proposed a novel conceptualization of AD as "type 3 diabetes", highlighting the critical roles insulin resistance impaired glucose metabolism pathogenesis disease. This article examines implications this association, exploring potential new avenues for treatment preventive strategies AD. Key evidence linking to emphasizes metabolic processes contribute neurodegeneration, including inflammation, oxidative stress, alterations signaling pathways. By framing within context, we can enhance our understanding its etiology, which turn may influence early diagnosis, plans, measures. Understanding manifestation opens up possibility employing therapeutic incorporate lifestyle modifications use antidiabetic medications mitigate cognitive decline. integrated approach improve patient outcomes deepen comprehension intricate relationship between neurodegenerative diseases disorders.

Language: Английский

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Mitochondrial DNA and Inflammation in Alzheimer’s Disease

Current Issues in Molecular Biology, Journal Year: 2023, Volume and Issue: 45(11), P. 8586 - 8606

Published: Oct. 25, 2023

Mitochondrial dysfunction and neuroinflammation are implicated in the pathogenesis of most neurodegenerative diseases, such as Alzheimer’s disease (AD). In fact, although a growing number studies show crosstalk between these two processes, there remain numerous gaps our knowledge mechanisms involved, which requires further clarification. On one hand, mitochondrial may lead to release damage-associated molecular patterns (mtDAMPs) recognized by microglial immune receptors contribute progression. other inflammatory molecules released glial cells can influence regulate function. A deeper understanding help identify biomarkers targets useful for treatment diseases. This review works published recent years is focused on description contribution neurodegeneration, with particular attention DNA (mtDNA) AD.

Language: Английский

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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

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Insulin resistance as the molecular link between diabetes and Alzheimer's disease

World Journal of Diabetes, Journal Year: 2024, Volume and Issue: 15(7), P. 1430 - 1447

Published: July 8, 2024

Diabetes mellitus (DM) and Alzheimer's disease (AD) are two major health concerns that have seen a rising prevalence worldwide. Recent studies indicated possible link between DM an increased risk of developing AD. Insulin, while primarily known for its role in regulating blood sugar, also plays vital protecting brain functions. Insulin resistance (IR), especially prevalent type 2 diabetes, is believed to play significant AD's development. When insulin signalling becomes dysfunctional, it can negatively affect various functions, making individuals more susceptible defining features, such as the buildup beta-amyloid plaques tau protein tangles. Emerging research suggests addressing insulin-related issues might help reduce or even reverse changes linked This review aims explore rela-tionship AD, with focus on IR. It explores molecular mechanisms by which IR lead assesses current treatments target Understanding IR's connection AD offers new possibilities highlights importance continued this interdisciplinary field.

Language: Английский

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A Tale of Two Diseases: Exploring Mechanisms Linking Diabetes Mellitus with Alzheimer’s Disease

Journal of Alzheimer s Disease, Journal Year: 2021, Volume and Issue: 85(2), P. 485 - 501

Published: Nov. 23, 2021

Dementias, including the type associated with Alzheimer’s disease (AD), are on rise worldwide. Similarly, 2 diabetes mellitus (T2DM) is one of most prevalent chronic diseases globally. Although mechanisms and treatments well-established for T2DM, there remains much to be discovered. Recent research efforts have further investigated factors involved in etiology AD. Previously perceived unrelated diseases, commonalities between T2DM AD more recently been observed. As a result, has labeled as “type 3 diabetes”. In this review, we detail shared processes that contribute these two diseases. Insulin resistance, main component pathogenesis also present AD, causing impaired brain glucose metabolism, neurodegeneration, cognitive impairment. Dysregulation insulin receptors components signaling pathway, protein kinase B, glycogen synthase 3β, mammalian target rapamycin reported both show evidence inflammation, oxidative stress, mitochondrial dysfunction, advanced glycation end products, amyloid deposition. The impact changes neurovascular structure genetics development conditions being examined. With discovery contributing innovative treatment approaches explored. Investigators evaluating efficacy various medications possible use but not limited glucagon-like peptide-1 receptor agonists peroxisome proliferator-activated receptor-gamma agonists. Furthermore, 136 active trials involving 121 therapeutic agents targeting novel biomarkers. efforts, step closer alleviating ravaging our communities.

Language: Английский

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Small-molecule drugs development for Alzheimer's disease

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: Nov. 1, 2022

Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative brain disorder with no effective therapeutic drugs currently. The complicated pathophysiology of AD not well understood, although beta-amyloid (Aβ) cascade and hyperphosphorylated tau protein were regarded as the two main causes AD. Other mechanisms, such oxidative stress, deficiency central cholinergic neurotransmitters, mitochondrial dysfunction, inflammation, also proposed studied targets in This review aims to summarize small-molecule that developed based on pathogenesis gives a deeper understanding We hope it could help scientists find new better treatments gradually conquer problems related future.

Language: Английский

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