Decoding Parkinson's Disease: The interplay of cell death pathways, oxidative stress, and therapeutic innovations.

Parkinson's disease (PD), a complex neurodegenerative disorder characterized by selective loss of substantia nigra (SN) dopaminergic neurons, pathological aggregation of α-synuclein (α-syn), and chronic neuroinflammation, is fundamentally driven by redox imbalance and oxidative stress. Recent studies reveal that a dynamic interplay of programmed and non-programmed cell death mechanisms-amplified by oxidative damage-drives PD progression. Programmed cell death pathways include apoptosis (caspase-dependent mitochondrial/extrinsic pathways), necroptosis (eceptor-interacting serine/threonine-protein kinase 1 (RIPK1)/RIPK3/mixed lineage kinase domain-like protein (MLKL) axis), pyroptosis (NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome/Gasdermin D (GSDMD)-mediated pore formation), PARthanatos (DNA damage-poly ADP-ribose polymerase (PARP-1)/apoptosis-inducing factor (AIF) cascade), ferroptosis (redox imbalance-driven lipid peroxidation/glutathione peroxidase 4 (GPX4) inactivation), disulfidptosis (disulfide stress from cystine metabolic collapse), and cuproptosis (mitochondrial lipoylated protein toxicity via copper-mediated oxidative damage), while non-programmed necrosis is triggered by energy collapse and calcium overload.

Cuproptosis-related genes associated with mitochondrial dysfunction in Parkinson's disease.

Parkinson's disease (PD), a neurodegenerative condition characterized by the loss of dopamine neurons and motor deficits, has recently been associated with cuproptosis, a process potentially leading to mitochondrial dysfunction. This study utilized six PD datasets from the GEO database, designating one for internal training and the remaining five for external validation. Various analytical methods, such as Gene Set Enrichment Analysis (GSEA), immune infiltration studies, and differential expression analysis, were employed to pinpoint differentially expressed genes (DEGs).

ACE2 Alleviates Microglia Neuroinflammation by RANK-RANKL-OPG Axis in Parkinson's Disease.

Parkinson's disease (PD) and osteoporosis are prevalent age-related conditions. Notably, individuals with PD exhibit a markedly elevated risk of osteoporosis and fractures. Osteoprotegerin (OPG), a critical regulator of bone homeostasis, may also influence neuroinflammatory processes.

Exploring Potential Causal Links: How Parkinson's Disease Brain Damage Impacts Liver Health-A Mendelian Randomization and Transcriptomic Study.

Background: Parkinson's disease (PD) is a common neurodegenerative disorder characterized by slow movements, muscle rigidity, tremors, and changes in gait and posture. Clinical studies have demonstrated a close association between PD and liver disease, but most research has focused on the impact of liver disorders on brain damage in PD, and further exploration is needed to understand the pathways and mechanisms underlying liver damage in patients with PD.

Methods: This study employs Mendelian Randomization (MR) and transcriptomic analysis to investigate the causal impact of PD-related brain damage on liver health, identifying serum metabolites (eg, cysteine) and shared immune-inflammatory pathways as mediators.

Bridging the Gap: The Neuro-immune Axis as a Key Player in Neurodegenerative Disorders.

Neurodegenerative diseases encompass a diverse array of disorders that have a profoundly detrimental impact on human health, characterized by their intricate and multifaceted pathogenesis. In the recent past, a growing body of scientific research has begun to shed light on the critical involvement of the neuro-immune axis in the onset and advancement of these debilitating conditions. This comprehensive review article delves into the intricate composition of the neuro-immune axis, elucidating the complex mechanisms through which it exerts its influence in the context of neurodegenerative diseases.

Synergistic pathways in Parkinson's disease: The promise of FGF21 and ACE2.

Parkinson's disease (PD), the second most prevalent neurodegenerative disorder globally, is pathologically characterized by progressive degeneration of dopaminergic neurons in the substantia nigra (SN). Current therapeutic strategies primarily alleviate clinical symptoms but lack efficacy in halting or reversing neurodegeneration. Recent studies have highlighted the FGF21-ACE2 signaling axis-a synergistic interaction between fibroblast growth factor 21 (FGF21) and angiotensin-converting enzyme 2 (ACE2)-as an emerging therapeutic target in PD due to its tripartite roles in neuroprotection, anti-inflammatory modulation, and metabolic homeostasis.

Beyond the Brain: Exploring the multi-organ axes in Parkinson's disease pathogenesis.

Background: Parkinson's Disease (PD), a complex neurodegenerative disorder, is increasingly recognized as a systemic condition involving multi-organ interactions. Emerging evidence highlights roles of organ-brain axes (lung-, liver-, heart-, muscle-, bone-, and gut-brain) in PD pathogenesis. These axes communicate via neural, circulatory, endocrine, and inflammatory pathways, collectively driving neurodegeneration.

Therapeutic applications of exercise in neurodegenerative diseases: focusing on the mechanism of SIRT1.

Neurodegenerative diseases comprise a group of central nervous system disorders marked by progressive neuronal degeneration and dysfunction. Their pathogenesis is multifactorial, involving oxidative stress, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. Recent research has highlighted the potential of exercise as a non-pharmacological intervention for both the prevention and treatment of these disorders.

Neuroprotective Effect of Abscisic Acid on MPTP-Induced Parkinson's Disease in Mice.

Parkinson's disease (PD) is the second largest neurodegenerative disease after Alzheimer's disease (AD), and neuroinflammation is one of its important causes. So far, there is no clear evidence that drugs can improve the onset of PD, so it is crucial to find and develop effective drugs for PD treatment. Abscisic acid (ABA) is a phytohormone with structural and medicinal functions similar to the PPAR-γ agonist thiazolidinedione drugs (TZDs).

Decreased Expression of Alzheimer's Disease-Related Genes in Cancer May Contribute to the Inverse-Relationship-a Computational Study.

Alzheimer's disease (AD) has been largely prevalent among the older population. With the increasing incidence of cancer over the years, scientists have explored the relationship between these two conditions which were formerly associated with aging. Interestingly, an inverse relationship between cancer and AD has been observed in large cohort studies which has garnered substantial interest.

Identification of NDUFV2, NDUFS7, OPA1, and NDUFA1 as biomarkers for Alzheimer's disease: Insights from oxidative stress and mitochondrial dysfunction in the hippocampus.

BackgroundAlzheimer's disease (AD) is characterized by amyloid-β deposits, neurofibrillary tangles, and hippocampal neurodegeneration, with oxidative stress and mitochondrial dysfunction playing critical roles in its pathogenesis. Identifying hub genes associated with these processes could advance biomarker discovery and therapeutic strategies.ObjectiveThis study aimed to identify key oxidative stress- and mitochondrial dysfunction-related genes in the AD hippocampus, evaluate their diagnostic potential, and explore therapeutic agents targeting these genes.

Parkinson's Disease: The Neurodegenerative Enigma Under the "Undercurrent" of Endoplasmic Reticulum Stress.

Parkinson's disease (PD), a prevalent neurodegenerative disorder, demonstrates the critical involvement of endoplasmic reticulum stress (ERS) in its pathogenesis. This review comprehensively examines the role and molecular mechanisms of ERS in PD. ERS represents a cellular stress response triggered by imbalances in endoplasmic reticulum (ER) homeostasis, induced by factors such as hypoxia and misfolded protein aggregation, which activate the unfolded protein response (UPR) through the inositol-requiring enzyme 1 (IRE1), protein kinase R-like endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6) pathways.

Target oxidative stress-induced disulfidptosis: novel therapeutic avenues in Parkinson's disease.

Background: Parkinson's disease (PD), a globally prevalent neurodegenerative disorder, has been implicated with oxidative stress (OS) as a central pathomechanism. Excessive reactive oxygen species (ROS) trigger neuronal damage and may induce disulfidptosis-a novel cell death modality not yet characterized in PD pathogenesis.

Method: Integrated bioinformatics analyses were conducted using GEO datasets to identify PD-associated differentially expressed genes (DEGs).

Bioinformatics screened of biomarkers for the prognosis of hepatocellular carcinoma.

BackgroundThis study aimed to identify hub genes linked to hepatocellular carcinoma (LIHC) pathogenesis using bioinformatics analysis.MethodA total of 3865 samples from 12 datasets in the HCCDB database were analyzed to identify prognostic expression genes (PDGs). Enrichment analysis using DAVID and GSCA databases unveiled biological processes and signaling pathways associated with PDGs.

The Power of Exercise: Unlocking the Biological Mysteries of Peripheral-Central Crosstalk in Parkinson's Disease.

Background: Exercise is a widely recognized non-pharmacological treatment for Parkinson's Disease (PD). The bidirectional regulation between the brain and peripheral organs has emerged as a promising area of research, with the mechanisms by which exercise impacts PD closely linked to the interplay between peripheral signals and the central nervous system.

Aim Of Review: This review aims to summarize the mechanisms by which exercise influences peripheral-central crosstalk to improve PD, discuss the molecular processes mediating these interactions, elucidate the pathways through which exercise may modulate PD pathophysiology, and identify directions for future research.

Evaluating the Molecular Interactions between Type 2 Diabetes Mellitus and Parkinson's Disease: Role of Antidiabetic Drugs as Promising Therapeutics.

Evidence from previous research demonstrates a relationship between diabetes mellitus (DM) and Parkinson's disease (PD). T2DM is associated with chronic glucose dysregulation, as an etiological factor. It inhibits neuronal function through disrupted insulin signaling and oxidative stress, which ultimately lead to the loss of dopaminergic neurons in the substantia nigra (SN).

Tectonic Characteristics of the Juyanhai Depression in the Yingen-Ejinaqi Basin, Inner Mongolia, China, Based on Gravity, Electrical, and Seismic Data.

To determine the tectonic characteristics of the Juyanhai Depression in the west of the Yingen-Ejinaqi Basin, gravity data in the study area were processed and analyzed on the basis of the collection of existing geophysical data. Then, fault systems in the Juyanhai Depression were comprehensively presumed and explained mainly using processed gravity data in conjunction with the electrical and seismic data. Existing tectonic units in the depression were divided and studied afterward.

Type 2 Diabetes Mellitus Exacerbates Pathological Processes of Parkinson's Disease: Insights from Signaling Pathways Mediated by Insulin Receptors.

Parkinson's disease (PD), a chronic and common neurodegenerative disease, is characterized by the progressive loss of dopaminergic neurons in the dense part of the substantia nigra and abnormal aggregation of alpha-synuclein. Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by chronic insulin resistance and deficiency in insulin secretion. Extensive evidence has confirmed shared pathogenic mechanisms underlying PD and T2DM, such as oxidative stress caused by insulin resistance, mitochondrial dysfunction, inflammation, and disorders of energy metabolism.

Unraveling the Bone-Brain Axis: A New Frontier in Parkinson's Disease Research.

Parkinson's disease (PD), as a widespread neurodegenerative disorder, significantly impacts patients' quality of life. Its primary symptoms include motor disturbances, tremor, muscle stiffness, and balance disorders. In recent years, with the advancement of research, the concept of the bone-brain axis has gradually become a focal point in the field of PD research.

The Role of ACE2 in Neurological Disorders: From Underlying Mechanisms to the Neurological Impact of COVID-19.

Angiotensin-converting enzyme 2 (ACE2) has become a hot topic in neuroscience research in recent years, especially in the context of the global COVID-19 pandemic, where its role in neurological diseases has received widespread attention. ACE2, as a multifunctional metalloprotease, not only plays a critical role in the cardiovascular system but also plays an important role in the protection, development, and inflammation regulation of the nervous system. The COVID-19 pandemic further highlights the importance of ACE2 in the nervous system.

Disulfidptosis: A New Target for Parkinson's Disease and Cancer.

Recent studies have uncovered intriguing connections between Parkinson's disease (PD) and cancer, two seemingly distinct disease categories. Disulfidptosis has garnered attention as a novel form of regulated cell death that is implicated in various pathological conditions, including neurodegenerative disorders and cancer. Disulfidptosis involves the dysregulation of intracellular redox homeostasis, leading to the accumulation of disulfide bonds and subsequent cell demise.

Innate neuroimmunity across aging and neurodegeneration: a perspective from amyloidogenic evolvability.

In Alzheimer's Disease (AD), amyloidogenic proteins (APs), such as β-amyloid (Aβ) and tau, may act as alarmins/damage-associated molecular patterns (DAMPs) to stimulate neuroinflammation and cell death. Indeed, recent evidence suggests that brain-specific type 2 immune networks may be important in modulating amyloidogenicity and brain homeostasis. Central to this, components of innate neuroimmune signaling, particularly type 2 components, assume distinctly specialized roles in regulating immune homeostasis and brain function.

Catalase immobilization: Current knowledge, key insights, applications, and future prospects - A review.

Catalase (CAT), a ubiquitous enzyme in all oxygen-exposed organisms, effectively decomposes hydrogen peroxide (HO), a harmful by-product, into water and oxygen, mitigating oxidative stress and cellular damage, safeguarding cellular organelles and tissues. Therefore, CAT plays a crucial role in maintaining cellular homeostasis and function. Owing to its pivotal role, CAT has garnered considerable interest.

The role of ACE2 in RAS axis on microglia activation in Parkinson's disease.

Background: The classic renin-angiotensin system (RAS) induces organ damage, while the ACE2/Ang-(1-7)/MasR axis opposes it. However, the role of ACE2 in the brain is unclear. We studied ACE2's role in the brain.