Mitochondrial transfer in tunneling nanotubes—a new target for cancer therapy

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: May 21, 2024

A century ago, the Warburg effect was first proposed, revealing that cancer cells predominantly rely on glycolysis during process of tumorigenesis, even in presence abundant oxygen, shifting main pathway energy metabolism from tricarboxylic acid cycle to aerobic glycolysis. Recent studies have unveiled dynamic transfer mitochondria within tumor microenvironment, not only between but also and stromal cells, immune others. In this review, we explore pathways mechanisms mitochondrial as well how these activities promote aggressiveness, chemotherapy resistance, evasion. Further, discuss research progress potential clinical significance targeting phenomena. We highlight therapeutic intercellular a future anti-cancer strategy enhancing cell-mediated immunotherapy.

Language: Английский

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GSK-3β: An exuberating neuroinflammatory mediator in Parkinson's disease

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 210, P. 115496 - 115496

Published: March 11, 2023

Neuroinflammation is a critical degradative condition affecting neurons in the brain. Progressive neurodegenerative conditions such as Alzheimer's disease and Parkinson's (PD) have been strongly linked to neuroinflammation. The trigger point for inflammatory cells body physiological immune system. response mediated by glial astrocytes can rectify alterations occurring cell time being but prolonged activation leads pathological progression. proteins mediating an response, per available literature, are undoubtedly GSK-3β, NLRP3, TNF, PPARγ, NF-κB, along with few other mediatory proteins. NLRP3 inflammasome undeniably principal instigator of neuroinflammatory regulatory pathways controlling its still unclear, besides less clarity interplay between different Recent reports suggested involvement GSK-3β regulating activation, exact mechanistic pathway remains vague. In current review, we attempt provide elaborate description crosstalk markers neuroinflammation progression, linking it transcription factors posttranslational modification recent clinical therapeutic advances targeting these also discussed parallel comprehensive view progress made PD management lacunas existing field.

Language: Английский

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Microtubule acetylation dyshomeostasis in Parkinson’s disease

Translational Neurodegeneration, Journal Year: 2023, Volume and Issue: 12(1)

Published: May 8, 2023

Abstract The inter-neuronal communication occurring in extensively branched neuronal cells is achieved primarily through the microtubule (MT)-mediated axonal transport system. This mechanistically regulated system delivers cargos (proteins, mRNAs and organelles such as mitochondria) back forth from soma to synapse. Motor proteins like kinesins dynein regulate polarized anterograde (from synapse) retrograde synapse soma) commute of cargos, respectively. Proficient by altering stability via post-translational modifications (PTMs) α- β-tubulin heterodimers, core components constructing MTs. Occurring within lumen MTs, K40 acetylation α-tubulin acetyl transferase its subsequent deacetylation HDAC6 SIRT2 are widely scrutinized PTMs that make MTs highly flexible, which turn promotes their lifespan. movement various motor proteins, including kinesin-1 (responsible for mitochondrial commute), enhanced this PTM, dyshomeostasis MT has been observed a variety neurodegenerative conditions, Alzheimer’s disease Parkinson’s (PD). PD second most common condition closely associated with impaired dynamics deregulated tubulin levels. Although relationship between status progression pathogenesis become chicken-and-egg question, our review aims provide insights into MT-mediated mitochondria PD. enzymatic regulators along synthetic modulators have also briefly explored. Moving towards tubulin-based therapy enhances could serve disease-modifying treatment neurological conditions lack it. Graphical abstract

Language: Английский

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Mitochondrial Complex I as a Pathologic and Therapeutic Target for Parkinson’s Disease

ACS Chemical Neuroscience, Journal Year: 2023, Volume and Issue: unknown

Published: March 29, 2023

The prevalence of Parkinson's disease (PD) continues to increase despite substantial research. Mounting evidence states that dysfunctional mitochondrial bioenergetics play a vital role in PD etiology. A disturbance the electron transport chain, more precisely, disruption complex I (MCI), is most detrimental factor. Due increased susceptibility toward MCI damage, dopaminergic neurons experience oxidative stress and compromise ATP production, leading neurodegeneration PD. This article reviews association with pathological mechanisms like α-synucleinopathy, neuroinflammation, stress, ER also describes potential therapeutic options explored overcome dysfunction related consequences.

Language: Английский

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Integration of miRNA’s theranostic potential with nanotechnology: Promises and challenges for Parkinson’s disease therapeutics

Mechanisms of Ageing and Development, Journal Year: 2023, Volume and Issue: 211, P. 111800 - 111800

Published: March 22, 2023

Language: Английский

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Mitochondrial transplantation exhibits neuroprotective effects and improves behavioral deficits in an animal model of Parkinson's disease

Neurotherapeutics, Journal Year: 2024, Volume and Issue: 21(4), P. e00355 - e00355

Published: April 4, 2024

Mitochondria are essential organelles for cell survival that manage the cellular energy supply by producing ATP. Mitochondrial dysfunction is associated with various human diseases, including metabolic syndromes, aging, and neurodegenerative diseases. Among diseases related to mitochondrial dysfunction, Parkinson's disease (PD) second most common characterized dopaminergic neuronal loss neuroinflammation. Recently, it was reported transfer between cells occurred naturally exogenous transplantation beneficial treating dysfunction. The current study aimed investigate therapeutic effect of on PD in vitro vivo. results showed PN-101 mitochondria isolated from mesenchymal stem exhibited a neuroprotective against 1-methyl-4-phenylpyridinium, 6-hydroxydopamine rotenone ameliorated brains C57BL/6J mice injected 30 ​mg/kg methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneally. In addition, anti-inflammatory effects reducing expression pro-inflammatory cytokines microglial suppressing activation striatum. Furthermore, intravenous treatment behavioral improvements during pole test rotarod MPTP-induced mice. These dual neuroprotection anti-neuroinflammation support potential as novel strategy PD.

Language: Английский

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Mitochondrial transplantation: A promising therapy for mitochondrial disorders

International Journal of Pharmaceutics, Journal Year: 2024, Volume and Issue: 658, P. 124194 - 124194

Published: May 3, 2024

Language: Английский

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Dimethyl fumarate ameliorates parkinsonian pathology by modulating autophagy and apoptosis via Nrf2-TIGAR-LAMP2/Cathepsin D axis

Brain Research, Journal Year: 2023, Volume and Issue: 1815, P. 148462 - 148462

Published: June 13, 2023

Language: Английский

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Involvement of Mitochondria in Parkinson’s Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(23), P. 17027 - 17027

Published: Dec. 1, 2023

Mitochondrial dysregulation, such as mitochondrial complex I deficiency, increased oxidative stress, perturbation of dynamics and mitophagy, has long been implicated in the pathogenesis PD. Initiating from observation that toxins cause PD-like symptoms DNA mutations are associated with risk PD, many mutated genes linked to familial forms including PRKN, PINK1, DJ-1 SNCA, have also found affect features. Recent research uncovered a much more involvement mitochondria Disruption quality control coupled abnormal secretion contents dispose damaged organelles may play role Furthermore, due its bacterial ancestry, circulating DNAs can function damage-associated molecular patterns eliciting inflammatory response. In this review, we summarize discuss connection between dysfunction highlighting triggers disease process, intra- extracellular roles PD well therapeutic potential transplantation.

Language: Английский

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Involvement of miRNA on epigenetics landscape of Parkinson's disease: From pathogenesis to therapeutics

Mechanisms of Ageing and Development, Journal Year: 2023, Volume and Issue: 213, P. 111826 - 111826

Published: May 31, 2023

Language: Английский

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