Phosphorylated Tau in Alzheimer’s Disease and Other Tauopathies

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(21), P. 12841 - 12841

Published: Oct. 25, 2022

Alzheimer’s disease (AD) is the leading cause of dementia in elderly people. Amyloid beta (Aβ) deposits and neurofibrillary tangles are major pathological features an brain. These proteins highly expressed nerve cells found most tissues. Tau primarily provides stabilization to microtubules part axons dendrites. However, tau a state becomes hyperphosphorylated, causing dysfunction synaptic impairment degeneration neurons. This article presents summary role tau, phosphorylated (p-tau) AD, other tauopathies. Tauopathies, including Pick’s disease, frontotemporal dementia, corticobasal degeneration, argyrophilic grain progressive supranuclear palsy, Huntington’s result misprocessing accumulation within neuronal glial cells. also focuses on current research post-translational modifications genetics pathology, tauopathies development new drugs targeting p-tau, therapeutics for treating possibly preventing

Language: Английский

---

Hyperphosphorylated tau (p-tau) and drug discovery in the context of Alzheimer's disease and related tauopathies

Drug Discovery Today, Journal Year: 2023, Volume and Issue: 28(3), P. 103487 - 103487

Published: Jan. 9, 2023

Language: Английский

---

Neuropathogenesis-on-chips for neurodegenerative diseases

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 12, 2024

Abstract Developing diagnostics and treatments for neurodegenerative diseases (NDs) is challenging due to multifactorial pathogenesis that progresses gradually. Advanced in vitro systems recapitulate patient-like pathophysiology are emerging as alternatives conventional animal-based models. In this review, we explore the interconnected pathogenic features of different types ND, discuss general strategy modelling NDs using a microfluidic chip, introduce organoid-on-a-chip next advanced relevant model. Lastly, overview how these models being applied academic industrial drug development. The integration chips, stem cells, biotechnological devices promises provide valuable insights biomedical research developing diagnostic therapeutic solutions NDs.

Language: Английский

---

Heavy metals: toxicity and human health effects

Archives of Toxicology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 20, 2024

Abstract Heavy metals are naturally occurring components of the Earth’s crust and persistent environmental pollutants. Human exposure to heavy occurs via various pathways, including inhalation air/dust particles, ingesting contaminated water or soil, through food chain. Their bioaccumulation may lead diverse toxic effects affecting different body tissues organ systems. The toxicity depends on properties given metal, dose, route, duration (acute chronic), extent bioaccumulation. detrimental impacts human health largely linked their capacity interfere with antioxidant defense mechanisms, primarily interaction intracellular glutathione (GSH) sulfhydryl groups (R-SH) enzymes such as superoxide dismutase (SOD), catalase, peroxidase (GPx), reductase (GR), other enzyme Although arsenic (As) is believed bind directly critical thiols, alternative hydrogen peroxide production processes have also been postulated. known signaling pathways affect a variety cellular processes, cell growth, proliferation, survival, metabolism, apoptosis. For example, cadmium can BLC-2 family proteins involved in mitochondrial death overexpression antiapoptotic Bcl-2 suppression proapoptotic (BAX, BAK) thus increasing resistance cells undergo malignant transformation. Nuclear factor erythroid 2-related 2 (Nrf2) an important regulator enzymes, level oxidative stress, oxidants has shown act double-edged sword response arsenic-induced stress. Another mechanism significant threats metal (e.g., Pb) involves substitution essential calcium (Ca), copper (Cu), iron (Fe)) structurally similar (Cd) (Pb)) metal-binding sites proteins. Displaced redox (copper, iron, manganese) from natural catalyze decomposition Fenton reaction generate damaging ROS hydroxyl radicals, causing damage lipids, proteins, DNA. Conversely, some metals, cadmium, suppress synthesis nitric oxide radical (NO · ), manifested by altered vasorelaxation and, consequently, blood pressure regulation. Pb-induced stress be indirectly responsible for depletion due its (O ·− resulting formation potent biological oxidant, peroxynitrite (ONOO − ). This review comprehensively discusses mechanisms effects. Aluminum (Al), (Cd), (As), mercury (Hg), (Pb), chromium (Cr) roles development gastrointestinal, pulmonary, kidney, reproductive, neurodegenerative (Alzheimer’s Parkinson’s diseases), cardiovascular, cancer (e.g. renal, lung, skin, stomach) diseases discussed. A short account devoted detoxification chelation use ethylenediaminetetraacetic acid ( EDTA), dimercaprol (BAL), 2,3-dimercaptosuccinic (DMSA), 2,3-dimercapto-1-propane sulfonic (DMPS), penicillamine chelators.

Language: Английский

---

Protection against Alzheimer's disease by luteolin: Role of brain glucose regulation, anti‐inflammatory activity, and the gut microbiota‐liver‐brain axis

BioFactors, Journal Year: 2020, Volume and Issue: 47(2), P. 218 - 231

Published: Dec. 21, 2020

Luteolin is a widely distributed flavone herbs and vegetables. It has anti-oxidant anti-inflammatory activities improves glucose metabolism by potentiating insulin sensitivity improving β-cell function mass. Alzheimer's disease (AD) induced the deposition of amyloid-beta (Aβ) in hippocampus formation neurotoxic Aβ plaques. The associated with increased from amyloid precursor protein up-regulation β-secretase β-site protein-cleaving enzyme 1 (BACE1). Furthermore, accumulation brain resistance. impairment insulin/IGF-1 signaling mainly resistance connected to signals originating liver gut microbiota, known as microbiota-liver-brain axis. This indicates that changes production short-chain fatty acids microbiota pro-inflammatory cytokines can alter brain. detected tissues after passing through blood-brain barrier, where it directly influence neuroinflammation modulate deposition. (10-70 mg/kg bw for rodents) systemic resistance, suppresses AD development directly, influences activation In this review, we evaluate potential luteolin mitigate two causes AD, neuroinflammatory processes, disruption review suggests intake enhance neuroinflammation, indirectly, protect against Alzheimer's-like disease, axis involved indirect pathway. However, most studies have been conducted animal studies, human clinical trials are needed.

Language: Английский

---

Role of Nrf2 in Synaptic Plasticity and Memory in Alzheimer’s Disease

Cells, Journal Year: 2021, Volume and Issue: 10(8), P. 1884 - 1884

Published: July 25, 2021

Nuclear factor erythroid 2-related 2 (Nrf2) is an important transcription that reduces oxidative stress. When reactive oxygen species (ROS) or nitrogen (RNS) are detected, Nrf2 translocates from the cytoplasm into nucleus and binds to antioxidant response element (ARE), which regulates expression of anti-inflammatory genes. impairments observed in majority neurodegenerative disorders, including Alzheimer’s disease (AD). The classic hallmarks AD include β-amyloid (Aβ) plaques, neurofibrillary tangles (NFTs). Oxidative stress early a novel therapeutic target for treatment AD. nuclear translocation impaired compared controls. Increased associated with memory synaptic plasticity. administration activators reverses plasticity rodent models Therefore, potential disorders

Language: Английский

---

Nanomaterials toward the treatment of Alzheimer’s disease: Recent advances and future trends

Chinese Chemical Letters, Journal Year: 2021, Volume and Issue: 32(6), P. 1857 - 1868

Published: Jan. 14, 2021

Language: Английский

---

Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets

Biomolecules, Journal Year: 2022, Volume and Issue: 12(11), P. 1676 - 1676

Published: Nov. 11, 2022

Damage or loss of brain cells and impaired neurochemistry, neurogenesis, synaptic nonsynaptic plasticity the lead to dementia in neurodegenerative diseases, such as Alzheimer's disease (AD). Injury synapses neurons accumulation extracellular amyloid plaques intracellular neurofibrillary tangles are considered main morphological neuropathological features AD. Age, genetic epigenetic factors, environmental stressors, lifestyle contribute risk AD onset progression. These factors associated with structural functional changes brain, leading cognitive decline. Biomarkers reflect cause specific function, especially pathways neurotransmission, neuroinflammation, bioenergetics, apoptosis, oxidative nitrosative stress. Even initial stages, is Aβ neurotoxicity, mitochondrial dysfunction, tau neurotoxicity. The integrative amyloid-tau-mitochondrial hypothesis assumes that primary neurotoxicity oligomers oligomers, their mutual synergy. For development new efficient drugs, targeting elimination potentiation effects, unwanted protein interactions biomarkers (mainly dysfunction) early stage seems promising.

Language: Английский

---

Roles of ApoE4 on the Pathogenesis in Alzheimer’s Disease and the Potential Therapeutic Approaches

Cellular and Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 43(7), P. 3115 - 3136

Published: May 25, 2023

Language: Английский

---

Exploring the role of COX-2 in Alzheimer's disease: Potential therapeutic implications of COX-2 inhibitors

Saudi Pharmaceutical Journal, Journal Year: 2023, Volume and Issue: 31(9), P. 101729 - 101729

Published: Aug. 7, 2023

This review highlights the potential role of cyclooxygenase-2 enzyme (COX-2) in pathogenesis Alzheimer's disease (AD) and therapeutic use non-steroidal anti-inflammatory drugs (NSAIDs) management AD. In addition to COX-2 enzymes inflammation, formation amyloid plaques neurofibrillary tangles brain, emphasizes that COXs-2 have a crucial normal synaptic activity plasticity, relationship with acetylcholine, tau protein, beta-amyloid (Aβ) which are main causes disease. Furthermore, points out kinase enzymes, including Cyclin Dependent Kinase 5 (CDK5) Glycogen Synthase 3β (GSK3β), known play phosphorylation strongly associated Therefore, like NSAIDs may be hopeful approach for managing However, results from studies examining effectiveness treating AD been mixed further research is needed fully understand mechanisms by involved development progression identify new strategies.

Language: Английский

---