Targeting natural antioxidant polyphenols to protect neuroinflammation and neurodegenerative diseases: a comprehensive review

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 24, 2025

Polyphenols, naturally occurring phytonutrients found in plant-based foods, have attracted significant attention for their potential therapeutic effects neurological diseases and neuroinflammation. These compounds possess diverse neuroprotective capabilities, including antioxidant, anti-inflammatory, anti-amyloid properties, which contribute to mitigating the progression of neurodegenerative conditions such as Alzheimer's Disease (AD), Parkinson's (PD), Dementia, Multiple Sclerosis (MS), Stroke, Huntington's (HD). Polyphenols been extensively studied ability regulate inflammatory responses by modulating activity pro-inflammatory genes influencing signal transduction pathways, thereby reducing neuroinflammation neuronal death. Additionally, polyphenols shown promise various cellular signaling pathways associated with viability, synaptic plasticity, cognitive function. Epidemiological clinical studies highlight polyphenol-rich diets decrease risk alleviate symptoms disorders Furthermore, demonstrated through regulation key Akt, Nrf2, STAT, MAPK, play critical roles neuroprotection body's immune response. This review emphasizes growing body evidence supporting combating neurodegeneration neuroinflammation, well enhancing brain health. Despite substantial promising hypotheses, further research investigations are necessary fully understand role establish them advanced targets age-related neuroinflammatory conditions.

Language: Английский

---

Brain network and energy imbalance in Parkinson’s disease: linking ATP reduction and α-synuclein pathology

Frontiers in Molecular Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: Jan. 22, 2025

Parkinson’s disease (PD) involves the disruption of brain energy homeostasis. This encompasses broad-impact factors such as mitochondrial dysfunction, impaired glycolysis, and other metabolic disturbances, like disruptions in pentose phosphate pathway purine metabolism. Cortical hubs, which are highly connected regions essential for coordinating multiple functions, require significant due to their dense synaptic activity long-range connections. Deficits ATP production PD can severely impair these hubs. The imbalance also affects subcortical regions, including massive axonal arbors striatum substantia nigra pars compacta neurons, high demand. decline may result α -synuclein accumulation, autophagy-lysosomal system impairment, neuronal network breakdown accelerated neurodegeneration. We propose an “ATP Supply–Demand Mismatch Model” help explain pathogenesis PD. model emphasizes how deficits drive pathological protein aggregation, autophagy, degeneration key networks, contributing both motor non-motor symptoms.

Language: Английский

---

A non‐redundant role of EAAT3 for ATP synthesis mediated by GDH in dopaminergic neuronal cells: a new avenue for glutamate metabolism and protection in Parkinson's disease

FEBS Journal, Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Parkinson's disease (PD) is a devastating neurodegenerative disorder with distinct loss of the nigrostriatal dopaminergic pathway. Despite multiplicity in etiology, alterations that disrupt neuronal integrity can be traced back to defects fundamental processes typically run under mitochondrial inputs. Evidence indicates activities are hierarchically integrated energetic performance these organelles, so an interesting perspective holds interventions aimed at improving bioenergetics potentially mitigate severity PD phenotype expression. In this mechanistic framework, approaches facilitate anaplerotic use glutamate (Glut) might counteract detrimental shift from Glut metabolism, which altered PD, excessive transmission feeds excitotoxicity and spiral. study, we investigated whether enhancement dehydrogenase (GDH) activity, by using GDH activator 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), has neuroprotective potential against injury. both retinoic acid-differentiated SH-SY5Y cells primary rat mesencephalic neurons challenged α-synuclein plus rotenone mimic BCH-dependent activation significantly ameliorated cell viability, improved ATP synthesis lessened control levels cellular redox burden. Strikingly, collected evidence for existence functional axis connecting activity specific intracellular pool Excitatory Amino Acid Transporters (EAATs), namely EAAT3. Overall, our results reveal novel non-redundant role EAAT3 GDH-dependent protection injury, may inspire new pharmacological pathology.

Language: Английский

---

Levodopa treatment: impacts and mechanisms throughout Parkinson’s disease progression

Journal of Neural Transmission, Journal Year: 2025, Volume and Issue: unknown

Published: April 11, 2025

Abstract Treatment with levodopa, a precursor of dopamine (DA), to compensate for the loss endogenous DA in Parkinson’s disease (PD), has been success story over 50 years. However, late stages PD, progressive degeneration dopaminergic neurons and ongoing reduction concentrations make it increasingly difficult maintain normal-like function. Typically, higher doses levodopa are required, fluctuations striatal concentrations—reflecting timing pattern administrations—become more pronounced. These can include highs that induce involuntary movements (levodopa-induced dyskinesia, LID) or lows result insufficient suppression PD symptoms (“OFF” phases). The enhanced primarily arise from buffering capacity, resulting neurons, an increased reliance on levodopa-derived release as “false neurotransmitter” by serotonergic neurons. In many patients, LID OFF-phases be alleviated modifying therapy provide continuous delivery using additional medications, such monoamine oxidase-B (MAO-B) inhibitors, amantadine, receptor agonists. Understanding challenges faced also requires considering striatum is characterized not only but neuroplastic adaptations PD-induced degenerations other neural populations. This review provides broad overview use treating focus underlying science encountered disease.

Language: Английский

---

Neuroprotective effects of GLP-1 class drugs in Parkinson’s disease

Frontiers in Neurology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 10, 2024

Parkinson’s disease (PD) is a chronic, progressive neurological disorder primarily affecting motor control, clinically characterized by resting tremor, bradykinesia, rigidity, and other symptoms that significantly diminish the quality of life. Currently, available treatments only alleviate without halting or delaying progression. There significant association between PD type 2 diabetes mellitus (T2DM), possibly due to shared pathological mechanisms such as insulin resistance, chronic inflammation, mitochondrial dysfunction. caused deficiency dopamine, neurotransmitter in brain plays critical role control movement. Glucose metabolism energy disorders also play an important pathogenesis PD. This review investigates neuroprotective glucagon-like peptide-1 (GLP-1) its receptor agonists, offering novel insights into potential therapeutic strategies for GLP-1 class drugs, used management, show promise addressing PD’s underlying pathophysiological mechanisms, including neuroprotection. These drugs can cross blood–brain barrier, improve stabilize function, enhance neuronal survival function. Additionally, they exhibit anti-inflammatory antioxidative stress effects, which are crucial neurodegenerative diseases like Research indicates agonists could both cognitive patients, marking breakthrough treatment prevention. Further exploration GLP-1’s molecular provide new preventive approaches, especially patients with concurrent T2DM. By targeting metabolic pathways, represent multifaceted approach treatment, hope better management improved patient outcomes.

Language: Английский

---

Dopamine and its precursor levodopa inactivate SARS-CoV-2 main protease by forming a quinoprotein

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 220, P. 167 - 178

Published: May 6, 2024

Language: Английский

---

No association between genetically predicted vitamin D levels and Parkinson’s disease

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(11), P. e0313631 - e0313631

Published: Nov. 15, 2024

Background Parkinson’s disease (PD) is a neurodegenerative disorder, primarily characterized by motor impairments. Vitamin D has several regulatory functions in nerve cell survival and gene expression via its receptors. Although research shown that vitamin deficiency prevalent among PD patients, the causal link to risk remains unclear. This study aims investigate relationship between using bidirectional two-sample Mendelian randomization (MR) analysis method. Methods applied MR explore PD. We selected statistically significant single nucleotide polymorphisms (SNPs) related 25-hydroxyvitamin (25(OH)D) as instrumental variables (IVs), ensuring no association with known confounders. The used GWAS data from over 1.2 million Europeans across four major published datasets, elucidating genetic correlation levels Results identified 148 SNPs associated 25(OH)D. After adjustment for confounding-related SNPs, 131 remained analysis. Data three cohorts revealed 25(OH)D IVW method ( P cohort1 = 0.365, cohort2 0.525, cohort3 0.117). reverse indicated insufficient evidence of causing decreased 0.776). Conclusion first use results indicate are not significantly causally at level. Therefore, future studies should exercise caution when investigating risk. While direct exists PD, this does preclude potential biomarker diagnosis. Furthermore, larger-scale longitudinal necessary evaluate diagnostic predictive value

Language: Английский

---

Glutathione S-transferase: A keystone in Parkinson's disease pathogenesis and therapy

Molecular and Cellular Neuroscience, Journal Year: 2024, Volume and Issue: unknown, P. 103981 - 103981

Published: Dec. 1, 2024

Language: Английский

---

Effects of psychological nursing in Parkinson's related depression patients undergoing functional magnetic resonance imaging: A randomized controlled trial

World Journal of Clinical Cases, Journal Year: 2024, Volume and Issue: 12(17), P. 3086 - 3093

Published: June 4, 2024

BACKGROUND Patients with Parkinson’s disease (PD) often experience depression, and some may require magnetic resonance imaging (MRI) for diagnosis, which can lead to MRI failure due claustrophobia. AIM To explore the value of psychological interventions in successfully completing functional scans brain PD-related depression. METHODS Ninety-six patients PD were randomly divided into two groups. The control group (47 patients) received general care, experimental (49 care combined care. Unified Parkinson's Disease Assessment Scale (UPDRS), Hamilton Depression (HAMD), Geriatric (GDS)-15 scores, heart rate, systolic blood pressure, MRI-Anxiety Questionnaire (MRI-AQ) scores before after scan recorded. completion rate (MR) scanning, scanning duration, image quality RESULTS Before no statistically significant difference was observed between groups terms UPDRS, HAMD, GDS-15, MRI-AQ scores. After score, time significantly lower than those group, whereas score higher group. CONCLUSION Psychological nursing are helpful alleviating depression assessing MR be successful patient's brain.

Language: Английский

---