Dementia and depression: Biological connections with amyloid β protein

Basic & Clinical Pharmacology & Toxicology, Journal Year: 2024, Volume and Issue: 134(5), P. 563 - 573

Published: March 8, 2024

Dementia is an umbrella term for a broad group of age-associated neurodegenerative diseases. It estimated that dementia affects 50 million people worldwide and Alzheimer's disease (AD) responsible up to 75% cases. Small extracellular senile plaques composed filamentous aggregates amyloid β (Aβ) protein tend bind neuronal receptors, affecting cholinergic, serotonergic, dopaminergic noradrenergic neurotransmission, leading neuroinflammation, among other pathophysiologic processes subsequent death, followed by dementia. The cascade hypothesis points pathological process in the cleavage precursor (APP), resulting Aβ. There close relationship between pathologies lead depression. depression prevalent 90% individuals diagnosed with Parkinson's disease, varying severity, 20 30% cases disease. hypothalamic pituitary adrenal (HPA) axis great intermediary pathophysiological mechanisms diseases This review discusses role Aβ depression, considering HPA axis, oxidative stress, signalling pathways neurotransmission.

Language: Английский

---

Developing Iron Nanochelating Agents: Preliminary Investigation of Effectiveness and Safety for Central Nervous System Applications

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 729 - 729

Published: Jan. 5, 2024

Excessive iron levels are believed to contribute the development of neurodegenerative disorders by promoting oxidative stress and harmful protein clustering. Novel chelation treatments that can effectively remove excess while minimizing negative effects on nervous system being explored. This study focuses creation evaluation innovative nanobubble (NB) formulations, shelled with various polymers such as glycol-chitosan (GC) conjugated deferoxamine (DFO), enhance their ability bind iron. Various methods were used evaluate physical chemical properties, capacity in diverse solutions impact reactive oxygen species (ROS). Notably, GC-DFO NBs demonstrated decrease amyloid-β misfolding caused To assess potential toxicity, vitro cytotoxicity testing was conducted using organotypic brain cultures from substantia nigra, revealing no adverse at appropriate concentrations. Additionally, spontaneous electrical signaling hippocampal neurons examined. Our findings suggest a novel nanochelation approach utilizing DFO-conjugated for removal cerebral regions, potentially preventing neurotoxic effects.

Language: Английский

---

Carbon Dots in the Pathological Microenvironment: ROS Producers or Scavengers?

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(29)

Published: July 22, 2024

Reactive oxygen species (ROS), as metabolic byproducts, play pivotal role in physiological and pathological processes. Recently, studies on the regulation of ROS levels for disease treatments have attracted extensive attention, mainly involving ROS-induced toxicity therapy mediated by producers antioxidant scavengers. Nanotechnology advancements led to development numerous nanomaterials with ROS-modulating capabilities, among which carbon dots (CDs) standing out noteworthy nanomedicines own their distinctive physicochemical properties, high stability, excellent biocompatibility. Despite progress treating ROS-related diseases based CDs, critical issues such rational design principles remain underexplored. The primary cause these may stem from intricate amalgamation core structure, defects, surface states, inherent poses challenges establishing a consistent generalization. This review succinctly summarizes recently ROS-modulated approaches using CDs treatment. Specifically, it investigates established therapeutic strategies CDs-regulated ROS, emphasizing interplay between intrinsic structure generation or scavenging ability. conclusion raises several unresolved key scientific prominent technological bottlenecks, explores future perspectives comprehensive CDs-based therapy.

Language: Английский

---

NOX-induced oxidative stress is a primary trigger of major neurodegenerative disorders

Progress in Neurobiology, Journal Year: 2023, Volume and Issue: 231, P. 102539 - 102539

Published: Oct. 12, 2023

Neurodegenerative diseases (NDDs) causing cognitive impairment and dementia are difficult to treat due the lack of understanding primary initiating factors. Meanwhile, major sporadic NDDs share many risk factors exhibit similar pathologies in their early stages, indicating existence common initiation pathways. Glucose hypometabolism associated with oxidative stress is one such primary, shared pathology, a likely cause detrimental disease-associated cascades; targeting this pathology may therefore be an effective preventative strategy for most NDDs. However, its exact trigger remain unclear. Recent research suggests that caused by NADPH oxidase (NOX) activation mechanism among could prove long-sought ubiquitous NDD trigger. We focus on two - Alzheimer's disease (AD) Parkinson's (PD), as well acquired epilepsy which increasingly recognized comorbidity also discuss available data suggesting relevance proposed mechanisms other delve into commonalities these neuroinflammation NOX involvement identify potential therapeutic targets gain deeper underlying causes

Language: Английский

---

Redox imbalance and metabolic defects in the context of Alzheimer disease

FEBS Letters, Journal Year: 2024, Volume and Issue: unknown

Published: March 12, 2024

Redox reactions play a critical role for intracellular processes, including pathways involved in metabolism and signaling. Reactive oxygen species (ROS) act either as second messengers or generators of protein modifications, fundamental mechanisms signal transduction. Disturbance redox homeostasis is associated with many disorders. Among these, Alzheimer's disease neurodegenerative pathology that presents hallmarks oxidative damage such increased ROS production, decreased activity antioxidant enzymes, modifications macromolecules, changes mitochondrial homeostasis. Interestingly, alteration closely defects energy metabolism, involving both carbohydrates lipids, the major fuels cell. As brain relies exclusively on glucose utilization represent harmful event brain. During aging, progressive perturbation occurs resulting hypometabolism. This condition contributes to increase neuronal cell vulnerability ultimately cognitive impairment. The current review discusses crosstalk between seems concert promoting neurodegeneration.

Language: Английский

---

The shift in the fatty acid composition of the circulating lipidome in Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(5), P. 3322 - 3333

Published: March 27, 2024

Fatty acids (FAs) are the building blocks of complex lipids and signaling compounds; role lipidome fatty acid profile (LFA) in AD progression remains unclear.

Language: Английский

---

Metabolic Features of Brain Function with Relevance to Clinical Features of Alzheimer and Parkinson Diseases

Molecules, Journal Year: 2022, Volume and Issue: 27(3), P. 951 - 951

Published: Jan. 30, 2022

Brain metabolism is comprised in Alzheimer’s disease (AD) and Parkinson’s (PD). Since the brain primarily relies on of glucose, ketone bodies, amino acids, aspects these metabolic processes disorders—and particularly how altered are related to oxidative and/or nitrosative stress resulting damaged targets—are reviewed this paper. Greater understanding decreased functions AD PD posited lead potentially important therapeutic strategies address both disorders, which cause relatively long-lasting quality life patients.

Language: Английский

---

Melatonin as a Mediator of the Gut Microbiota–Host Interaction: Implications for Health and Disease

Antioxidants, Journal Year: 2023, Volume and Issue: 13(1), P. 34 - 34

Published: Dec. 23, 2023

In recent years, the role played by melatonin on gut microbiota has gained increasingly greater attention. Additionally, been proposed as an alternative source of melatonin, suggesting that this antioxidant indoleamine could act a sort messenger between and host. This review analyses available scientific literature about possible mechanisms involved in mediating role, highlighting its effects influence interaction. addition, we also knowledge composition, well ability to alleviate dysbiosis related sleep deprivation or chronodisruptive conditions. The melatonin–gut relationship discussed terms development different disorders, from inflammatory metabolic disorders psychiatric neurological conditions, considering oxidative stress reactive oxygen species-scavenging properties main factors relationship.

Language: Английский

---

Research Progress on the Mechanisms of Protocatechuic Acid in the Treatment of Cognitive Impairment

Molecules, Journal Year: 2024, Volume and Issue: 29(19), P. 4724 - 4724

Published: Oct. 6, 2024

Cognitive impairment (CI) is a type of mental health disorder that mainly affects cognitive abilities, such as learning, memory, perception, and problem-solving. Currently, in clinical practice, the treatment focuses on application cholinesterase inhibitors NMDA receptor antagonists; however, there no specific effective drug yet. Procatechuic acid (PCA) possesses various functions, including antibacterial, antiasthmatic, expectorant effects. In recent years, it has received growing attention domain. Therefore, by summarizing mechanisms action procatechuic this paper, found multiple effects, regulating expression neuroprotective factors, inhibiting cell apoptosis, promoting autophagy-lysosome pathway, suppressing oxidative stress damage, inflammatory responses, improving synaptic plasticity dysfunction, Aβ deposition, reducing APP hydrolysis, enhancing cholinergic system, excitotoxicity neuronal cells. The involved signaling pathways include activating Pi3K-akt-mTor JNK, P38 MAPK, P38-ERK-JNK, SIRT1, NF-κB/p53, etc. This paper aims to present latest progress research acid, aspects its chemical properties, sources, pharmacokinetics, for treating neurodegenerative diseases.

Language: Английский

---

Natural Products and Their Neuroprotective Effects in Degenerative Brain Diseases: A Comprehensive Review

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(20), P. 11223 - 11223

Published: Oct. 18, 2024

As the global population ages, incidence of neurodegenerative diseases such as Alzheimer’s and Parkinson’s is rapidly rising. These present a significant public health challenge, they severely impair cognitive motor functions, ultimately leading to substantial reduction in quality life placing heavy burden on healthcare systems worldwide. Although several therapeutic agents have been developed manage symptoms these diseases, their effectiveness often limited, there remains an urgent need for preventive strategies. Growing evidence indicates that bioactive compounds from natural products possess neuroprotective properties through antioxidant anti-inflammatory effects, modulating key pathways phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) brain-derived neurotrophic factor–tropomyosin receptor B–cAMP response element-binding protein (BDNF-TrkB-CREB), which are crucial neuronal survival. may also reduce amyloid-beta tau pathology, well enhance cholinergic neurotransmission by inhibiting acetylcholinesterase activity. By targeting oxidative stress, neuroinflammation, neurodegeneration, offer promising approach both prevention treatment. findings suggest be preventing treating diseases. This review aims explore pathogenesis limitations current therapies, potential role agents.

Language: Английский

---