Calcium bridges built by mitochondria-associated endoplasmic reticulum membranes: potential targets for neural repair in neurological diseases DOI Creative Commons

Yichen Peng,

Li Zhou,

Yaju Jin

et al.

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(12), P. 3349 - 3369

Published: Nov. 13, 2024

The exchange of information and materials between organelles plays a crucial role in regulating cellular physiological functions metabolic levels. Mitochondria-associated endoplasmic reticulum membranes serve as physical contact channels the membrane mitochondrial outer membrane, formed by various proteins protein complexes. This microstructural domain mediates several specialized functions, including calcium (Ca 2+ ) signaling, autophagy, morphology, oxidative stress response, apoptosis. Notably, dysregulation Ca signaling mediated mitochondria-associated is critical factor pathogenesis neurological diseases. Certain or complexes within these directly indirectly regulate distance mitochondria, well transduction signaling. Conversely, influences other membrane-associated functions. These can vary significantly across different diseases—such ischemic stroke, traumatic brain injury, Alzheimer’s disease, Parkinson’s amyotrophic lateral sclerosis, Huntington’s disease—and their respective stages progression. Targeted modulation disease-related pathways functional enhance function promote regeneration repair damaged neurons. Therefore, membranes-mediated pivotal pathological progression diseases represents significant potential therapeutic target. review focuses on effects distinct roles diseases, specifically highlighting early protective neuronal damage that result from prolonged overload deficiency. article provides comprehensive analysis mechanisms contributing to exploration targets for promoting neuroprotection nerve repair.

Language: Английский

Synaptic plasticity and neuroprotection: The molecular impact of flavonoids on neurodegenerative disease progression DOI

Spandana Rajendra Kopalli,

Tapan Behl,

Ashishkumar Kyada

et al.

Neuroscience, Journal Year: 2025, Volume and Issue: 569, P. 161 - 183

Published: Feb. 7, 2025

Language: Английский

Citations

1
Cracking the Endothelial Calcium (Ca2+) Code: A Matter of Timing and Spacing DOI Open Access
Francesco Moccia,

Valentina Brunetti,

Teresa Soda

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(23), P. 16765 - 16765

Published: Nov. 26, 2023

A monolayer of endothelial cells lines the innermost surface all blood vessels, thereby coming into close contact with every region body and perceiving signals deriving from both bloodstream parenchymal tissues. An increase in intracellular Ca2+ concentration ([Ca2+]i) is main mechanism whereby vascular integrate information conveyed by local circulating cues. Herein, we describe dynamics spatial distribution to understand how an array spatially restricted (at subcellular cellular levels) exploited intima fulfill this complex task. We then illustrate affect most appropriate function are integrated transmit more distant sites maintain cardiovascular homeostasis. Vasorelaxation sprouting angiogenesis were selected as example functions that finely tuned variable spatio-temporal profile signals. further highlighted distinct signatures regulate different phases vasculogenesis, i.e., proliferation migration, precursors.

Language: Английский

Citations

13
Two Signaling Modes Are Better than One: Flux-Independent Signaling by Ionotropic Glutamate Receptors Is Coming of Age DOI Creative Commons

Valentina Brunetti,

Teresa Soda, Roberto Berra‐Romani

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(4), P. 880 - 880

Published: April 16, 2024

Glutamate is the major excitatory neurotransmitter in central nervous system. Glutamatergic transmission can be mediated by ionotropic glutamate receptors (iGluRs), which mediate rapid synaptic depolarization that associated with Ca2+ entry and activity-dependent change strength of transmission, as well metabotropic (mGluRs), slower postsynaptic responses through recruitment second messenger systems. A wealth evidence reported over last three decades has shown this dogmatic subdivision between iGluRs mGluRs may not reflect actual physiological signaling mode iGluRs, i.e., α-amino-3-hydroxy-5-methyl-4-isoxasolepropionic acid (AMPA) (AMPAR), kainate (KARs), N-methyl-D-aspartate (NMDA) (NMDARs). Herein, we review available supporting notion canonical recruit flux-independent pathways only neurons, but also brain astrocytes cerebrovascular endothelial cells. Understanding versatility exert a profound impact on our understanding glutamatergic synapses. Furthermore, it shed light novel neuroprotective strategies against disorders.

Language: Английский

Citations

4
Nitrogen doped carbon dots for in vitro intracellular redox modulation via optical stimulation DOI Creative Commons
Paola Lagonegro, Camilla Marzuoli, Gabriele Tullii

et al.

Journal of Materials Chemistry B, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Carbon dots (CDs) are promising candidates as oxygen photosensitizers, in cancer therapeutic applications due to their high quantum yield, superior chemical and photostability, low cytotoxicity ease of functionalization/tuning.

Language: Английский

Citations

0
Lysosome-Mitochondrial Crosstalk in Cellular Stress and Disease DOI Creative Commons

Szilvia Kiraly,

Jack Stanley, Emily R. Eden

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(2), P. 125 - 125

Published: Jan. 22, 2025

The perception of lysosomes and mitochondria as entirely separate independent entities that degrade material produce ATP, respectively, has been challenged in recent years not only more complex roles for both organelles, but also an unanticipated level interdependence are being uncovered. Coupled lysosome mitochondrial function dysfunction involve crosstalk between the two organelles which goes beyond quality control lysosome-mediated clearance damaged through mitophagy. Our understanding these essential metabolic transformed by major advances field membrane contact sites biology. We now know play central inter-organelle communication. This importance mitochondria–lysosome contacts (MLCs) cellular homeostasis, evinced growing number diseases have associated with their dysregulation, is starting to be appreciated. How MLCs regulated how coordination other pathways lysosome–mitochondria achieved subjects ongoing scrutiny, this review explores current governing its impact on stress disease.

Language: Английский

Citations

0
Ca2+ Signaling in Cardiac Fibroblasts: An Emerging Signaling Pathway Driving Fibrotic Remodeling in Cardiac Disorders DOI Creative Commons
Francesco Moccia, Antonio Totaro, Germano Guerra

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 734 - 734

Published: March 17, 2025

Cardiac fibrosis is a scarring event that occurs in the myocardium response to multiple cardiovascular disorders, such as acute myocardial infarction (AMI), ischemic cardiomyopathy, dilated hypertensive heart disease, inflammatory diabetic and aortic stenosis. Fibrotic remodeling mainly sustained by differentiation of fibroblasts into myofibroblasts, which synthesize secrete most extracellular matrix (ECM) proteins. An increase intracellular Ca2+ concentration ([Ca2+]i) cardiac emerging critical mediator fibrogenic signaling cascade. Herein, we review mechanisms may shape signals involved fibroblast transdifferentiation myofibroblasts. We focus our attention on functional interplay between inositol-1,4,5-trisphosphate (InsP3) receptors (InsP3Rs) store-operated entry (SOCE). In accordance with this, InsP3Rs SOCE drive elicited Gq-protein coupled (GqPCRs) promote fibrotic remodeling. Then, describe additional sustain entry, including receptor-operated (ROCE), P2X receptors, Transient Receptor Potential (TRP) channels, Piezo1 channels. parallel, discuss pharmacological manipulation handling machinery promising approach mitigate or reverse disorders.

Language: Английский

Citations

0
Mitochondrial heat production: the elephant in the lab… DOI Creative Commons
Pierre Rustin, Howard T. Jacobs, Mügen Terzioglu

et al.

Trends in Biochemical Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Alterations in Proteostasis Mechanisms in Niemann–Pick Type C Disease DOI Open Access

Iris Valeria Servín Muñoz,

Daniel Ortuño‐Sahagún, Christian Griñán‐Ferré

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3806 - 3806

Published: March 29, 2024

Niemann-Pick Type C (NPC) represents an autosomal recessive disorder with incidence rate of 1 in 150,000 live births, classified within lysosomal storage diseases (LSDs). The abnormal accumulation unesterified cholesterol characterizes the pathophysiology NPC. This phenomenon is not unique to NPC, as analogous accumulations have also been observed Alzheimer's disease, Parkinson's and other neurodegenerative disorders. Interestingly, disturbances folding mutant protein NPC1 I1061T are accompanied by aggregation proteins such hyperphosphorylated tau, α-synuclein, TDP-43, β-amyloid peptide. These suggest potential disruptions proteostasis, a regulatory process encompassing four principal mechanisms: synthesis, folding, maintenance degradation. dysregulation these processes leads excessive that impair cell function trigger cytotoxicity. comprehensive review delineates reported alterations across proteostasis mechanisms changes from synthesis Additionally, it discusses therapeutic interventions targeting pharmacological facets Noteworthy among valproic acid, histone deacetylase inhibitor (HDACi) modulates acetylation during synthesis. In addition, various options addressing modulation, abiraterone acetate, DHBP, calnexin, arimoclomol, examined. treatments impeding degradation, exemplified bortezomib MG132, explored strategies. consolidates current knowledge on NPC underscores landscape diverse this intricate process.

Language: Английский

Citations

3
Cognitive Impairment and Synaptic Dysfunction in Cardiovascular Disorders: The New Frontiers of the Heart–Brain Axis DOI Creative Commons
Teresa Soda, Teresa Pasqua, Giovambattista De Sarro

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(10), P. 2387 - 2387

Published: Oct. 18, 2024

Within the central nervous system, synaptic plasticity, fundamental to processes like learning and memory, is largely driven by activity-dependent changes in strength. This plasticity often manifests as long-term potentiation (LTP) depression (LTD), which are bidirectional modulations of efficacy. Strong epidemiological experimental evidence show that heart-brain axis could be severely compromised both neurological cardiovascular disorders. Particularly, disorders, such heart failure, hypertension, obesity, diabetes insulin resistance, arrhythmias, may lead cognitive impairment, a condition known cardiogenic dementia. Herein, we review available knowledge on molecular mechanisms dementia arise describe how LTP and/or LTD induction maintenance CA1 region hippocampus metabolic syndrome, arrhythmias. We also discuss emerging endothelial dysfunction contribute directly altering hippocampal impairing synaptically induced activation nitric oxide synthase. A better understanding CV disorders impact proper function synapses will shed novel light underpinnings dementia, thereby providing new perspective for more specific pharmacological treatments.

Language: Английский

Citations

3
Lysosomal TRPML1 triggers global Ca2+ signals and nitric oxide release in human cerebrovascular endothelial cells DOI Creative Commons

Valentina Brunetti,

Roberto Berra‐Romani, Filippo Conca

et al.

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

Published: June 21, 2024

Lysosomal Ca

Citations

1