Peripheral Blood Immune Cells from Individuals with Parkinson's Disease or Inflammatory Bowel Disease Share Deficits in Iron Storage and Transport that are Modulated by Non-Steroidal Anti-Inflammatory Drugs DOI Creative Commons
MacKenzie L. Bolen, Beatriz Maffini Gomes, B. Gill

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 19, 2024

ABSTRACT Parkinson’s Disease (PD) is a multisystem disorder in which dysregulated neuroimmune crosstalk and inflammatory relay via the gut-blood-brain axis have been implicated PD pathogenesis. Although alterations circulating cytokines reactive oxygen species (ROS) associated with PD, no biomarkers identified that predict clinical progression or disease outcome. Gastrointestinal (GI) dysfunction, involves perturbation of underlying immune system, an early often-overlooked symptom affects up to 80% individuals living PD. Interestingly, 50-70% bowel (IBD), GI condition has epidemiologically linked display chronic illness-induced anemia — drives toxic accumulation iron gut. Ferroptotic (or loaded) cells small dysmorphic mitochondria—suggesting mitochondrial dysfunction consequence accumulation. In pro-inflammatory environments, accumulates cells, suggesting possible connection and/or synergy between dysregulation cell dysfunction. Peripheral blood mononuclear (PBMCs) recapitulate certain PD-associated neuropathological signatures can act as communicating messengers gut-brain axis. Additionally, this communication be modulated by several environmental factors; specifically, our data further support existing literature demonstrating role for non-steroidal anti-inflammatory drugs (NSAIDs) modulating transcriptional states inflamed individuals. A mechanism linking gut inflammation function within peripheral yet conferring risk To end, we isolated PBMCs simultaneously evaluated their directed transcriptome bioenergetic status, investigate if sensitization are IBD because remittent activation. We shared features immunometabolism may contribute epidemiological association reported

Язык: Английский

Peripheral blood immune cells from individuals with Parkinson's disease or inflammatory bowel disease share deficits in iron storage and transport that are modulated by non-steroidal anti-inflammatory drugs DOI Creative Commons
MacKenzie L. Bolen, Beatriz Maffini Gomes, B. Gill

и другие.

Neurobiology of Disease, Год журнала: 2025, Номер unknown, С. 106794 - 106794

Опубликована: Янв. 1, 2025

Parkinson's Disease (PD) is a multisystem disorder in which dysregulated neuroimmune crosstalk and inflammatory relay via the gut-blood-brain axis have been implicated PD pathogenesis. Although alterations circulating cytokines reactive oxygen species (ROS) associated with PD, no biomarkers identified that predict clinical progression or disease outcome. Gastrointestinal (GI) dysfunction, involves perturbation of underlying immune system, an early often-overlooked symptom affects up to 80 % individuals living PD. Interestingly, 50-70 bowel (IBD), GI condition has epidemiologically linked display chronic illness-induced anemia - drives toxic accumulation iron gut. Ferroptotic (or loaded) cells small dysmorphic mitochondria-suggesting mitochondrial dysfunction consequence accumulation. In pro-inflammatory environments, accumulates cells, suggesting possible connection and/or synergy between dysregulation cell dysfunction. Peripheral blood mononuclear (PBMCs) recapitulate certain PD-associated neuropathological signatures can act as communicating messengers gut-brain axis. Additionally, this communication be modulated by several environmental factors; specifically, our data further support existing literature demonstrating role for non-steroidal anti-inflammatory drugs (NSAIDs) modulating transcriptional states inflamed individuals. A mechanism linking gut inflammation function within peripheral yet conferring risk To end, we isolated PBMCs simultaneously evaluated their directed transcriptome bioenergetic status, investigate if sensitization are IBD because remittent activation. We shared features immunometabolism may contribute epidemiological association reported

Язык: Английский

Процитировано

0
Calcium-iron crosstalk in epileptogenesis: Unraveling mechanisms and therapeutic opportunities DOI Creative Commons
Li Xuan,

Ao-Long Tao,

Nayiyuan Wu

и другие.

Neurobiology of Disease, Год журнала: 2025, Номер unknown, С. 106989 - 106989

Опубликована: Июнь 1, 2025

Epilepsy, a chronic neurological disorder affecting millions globally, remains poorly understood in its etiology and therapeutic management. Emerging evidence highlights the intricate interplay between calcium (Ca2+) iron (Fe2+/Fe3+) ions modulating neuronal excitability, oxidative stress, synaptic plasticity-key processes implicated epileptogenesis. This review synthesizes current knowledge on dual roles of Ca2+ Fe2+/Fe3+ epilepsy, emphasizing their bidirectional regulatory mechanisms pathological synergism. Calcium dysregulation, mediated through voltage-gated channels (e.g., Cav1.2, Cav3.2), store-operated entry (SOCE), mitochondrial uniporters (MCU), exacerbates hyperexcitability seizure propagation. Concurrently, overload drives ferroptosis via lipid peroxidation glutathione depletion, while deficiency impairs neurodevelopmental processes. Crucially, Ca2+-Fe2+ crosstalk intersects at multiple nodes: TRP TRPC6, TRPML1) facilitate ion transport; dysfunction links with Fe2+-dependent ROS generation; inflammatory cascades disrupt both homeostasis. Clinically, antiepileptic drugs targeting ethosuximide, zonisamide) emerging inhibitors deferoxamine, RTA 408) underscore potential these pathways. However, drug resistance incomplete control necessitate novel strategies leveraging interaction networks. We propose that combinatorial approaches signaling hubs-such as MCU-TRPML1 axes or redox-sensitive RyR channels-may offer synergistic benefits. Future research must prioritize cross-model validation, advanced neuroimaging biomarkers, multidisciplinary frameworks to translate mechanistic insights into precision therapies. comprehensive analysis positions pivotal frontier epilepsy research, bridging molecular pathophysiology innovative treatment paradigms.

Язык: Английский

Процитировано

0
IL-6 and diabetic kidney disease DOI Creative Commons
Lei Zhang,

Futian Xu,

Liyan Hou

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Дек. 19, 2024

Diabetic kidney disease (DKD) is a severe microvascular complication of diabetes associated with high mortality and disability rates. Inflammation has emerged as key pathological mechanism in DKD, prompting interest novel therapeutic approaches targeting inflammatory pathways. Interleukin-6 (IL-6), well-established cytokine known for mediating various responses, attracted great attention the DKD field. Although multiple

Язык: Английский

Процитировано

3
Peripheral Blood Immune Cells from Individuals with Parkinson's Disease or Inflammatory Bowel Disease Share Deficits in Iron Storage and Transport that are Modulated by Non-Steroidal Anti-Inflammatory Drugs DOI Creative Commons
MacKenzie L. Bolen, Beatriz Maffini Gomes, B. Gill

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 19, 2024

ABSTRACT Parkinson’s Disease (PD) is a multisystem disorder in which dysregulated neuroimmune crosstalk and inflammatory relay via the gut-blood-brain axis have been implicated PD pathogenesis. Although alterations circulating cytokines reactive oxygen species (ROS) associated with PD, no biomarkers identified that predict clinical progression or disease outcome. Gastrointestinal (GI) dysfunction, involves perturbation of underlying immune system, an early often-overlooked symptom affects up to 80% individuals living PD. Interestingly, 50-70% bowel (IBD), GI condition has epidemiologically linked display chronic illness-induced anemia — drives toxic accumulation iron gut. Ferroptotic (or loaded) cells small dysmorphic mitochondria—suggesting mitochondrial dysfunction consequence accumulation. In pro-inflammatory environments, accumulates cells, suggesting possible connection and/or synergy between dysregulation cell dysfunction. Peripheral blood mononuclear (PBMCs) recapitulate certain PD-associated neuropathological signatures can act as communicating messengers gut-brain axis. Additionally, this communication be modulated by several environmental factors; specifically, our data further support existing literature demonstrating role for non-steroidal anti-inflammatory drugs (NSAIDs) modulating transcriptional states inflamed individuals. A mechanism linking gut inflammation function within peripheral yet conferring risk To end, we isolated PBMCs simultaneously evaluated their directed transcriptome bioenergetic status, investigate if sensitization are IBD because remittent activation. We shared features immunometabolism may contribute epidemiological association reported

Язык: Английский

Процитировано

1