Recent advances in mitochondrial diseases: From molecular insights to therapeutic perspectives

Aldossary, Ahmad M.; Tawfik, Essam A.; Alomary, Mohammed N.; Alsudir, Samar A.; Alfahad, Ahmed J.; Alshehri, Abdullah A.; Almughem, Fahad A.; Mohammed, Rean; Alzaydi, Mai M.

doi:10.1016/j.jsps.2022.05.011

Cited by 11 publications

(5 citation statements)

References 186 publications

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“…Unfortunately, the precise cause of this genotoxic impact is still unknown. The direct effects of NPs on genomic materials, including ROS production and DNA/chromosome damage, are currently the focus of much study [ 194 , 195 ]. A study discovered that the presence of gold nanoparticles measuring 10 nm altered these markers significantly in rat organs, indicating that they interfere with the antioxidant defense mechanism.…”

Section: Metal Nanoparticle Potential Cytotoxicitymentioning

confidence: 99%

Nanomaterials in the Wound Healing Process: New Insights and Advancements

Sangnim,

Puri,

Dheer

et al. 2024

Pharmaceutics

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Wounds, which are becoming more common as a result of traumas, surgery, burns, and chronic illnesses like diabetes, remain a critical medical problem. Infectious bacteria impact the healing process, particularly if its biofilm (biological films) leads to a prolonged effect. Nanomaterials have emerged as promising candidates in the field of wound healing due to their unique properties and versatile applications. New insights into the interactions between nanomaterials and wound microenvironments have shed light on the mechanisms underlying their therapeutic effects. However, a significantly minimal amount of research has been carried out to see if these nanomaterials significantly promote the wound healing process. In this review, we provided an outline of the various types of nanomaterials that have been studied for healing wounds and infection prevention. Overall, the utilization of nanomaterials in wound healing holds great promise and continues to evolve, providing new opportunities for the development of effective and efficient wound care therapies.

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Section: Metal Nanoparticle Potential Cytotoxicitymentioning

confidence: 99%

Nanomaterials in the Wound Healing Process: New Insights and Advancements

Sangnim,

Puri,

Dheer

et al. 2024

Pharmaceutics

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“…El síndrome de Leigh (OMIM#256000, SL) es una rara enfermedad neurodegenerativa, potencialmente mortal, causada por mutaciones de genes en las proteínas codificadas por el genoma nuclear o mitocondrial en la vía de la fosforilación oxidativa (OXPHOS), las cuales ocasionan una disfunción del metabolismo energético mitocondrial (1,2). Afecta a alrededor de 1 de cada 30.000 a 40.000 recién nacidos (2,3).…”

Section: Introductionunclassified

“…Su primera descripción data de 1951 por el neuropatólogo Denis Archibald Leigh, quien hizo una correlación anatomo-patológica y un análisis post mortem en pacientes con encefalopatía subaguda de curso severo, progresivo y letal; en 1977 se hizo su primera asociación con disfunción de la cadena respiratoria, y posteriormente se publicaron artículos que completaron la descripción clínica de un síndrome neurodegenerativo. La tomografía computarizada (TC) y la resonancia magnética (RM) cerebral muestran lesiones núcleo basales características y el tallo cerebral, y los estudios genéticos permiten identificar las variantes patogénicas en el ADN mitocondrial y nuclear (1).…”

Section: Introductionunclassified

Caso de curso letal de mutación homocigota del gen nuclear mitocondrial hidroxiisobutiril-CoA hidrolasa HIBCH

Fernández Cruz,

Ortiz Giraldo

2024

Acta Neurol Colomb

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Introducción: el síndrome de Leigh (SL) es una enfermedad neurodegenerativa infrecuente que afecta principalmente a lactantes y a escolares, ocasionada por una mutación en genes involucrados en la vía de la fosforilación oxidativa y cuyo déficit produce una disfunción en el metabolismo energético mitocondrial. Clínicamente, se caracteriza por un rápido deterioro neurológico, hallazgos típicos en neuroimagen y marcadores bioquímicos que orientan en su reconocimiento. En la mayoría de los pacientes tiene un curso progresivo y mortalidad temprana. Presentación del caso: se presenta el caso de una lactante de 5 meses que presenta perdida de los hitos del desarrollo. Los paraclínicos mostraron lactoacidosis, en neuroimagen necrosis nucleobasal, y la secuenciación genómica completa puso en evidencia una mutación homocigota del gen nuclear mitocondrial de la enzima 3-hidroxiisobutiril-CoA hidrolasa HIBCH. La paciente evolucionó con epilepsia refractaria, movimientos anormales, síndrome de West, apneas y falleció a los 10 meses de vida por insuficiencia respiratoria aguda. Discusión: el SL es con frecuencia una enfermedad rápidamente progresiva, que puede ser causada por errores innatos del metabolismo como la mutación del gen de la enzima HIBCH. El diagnóstico confirmatorio se hace con secuenciación exómica o genómica masiva y su manejo consiste en el tratamiento de los síntomas, modificaciones nutricionales, cuidado paliativo y consejería genético-reproductiva. Conclusión: el SL por mutaciones en el gen HIBCH es una enfermedad neurodegenerativa con síntomas variables, que afecta el desarrollo motor e intelectual. El diagnóstico se basa en biología molecular. El tratamiento actual busca aliviar síntomas y ajustar la nutrición, evidenciando desafíos inherentes a errores innatos del metabolismo.

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“…The lack of effective treatments for mitochondrial disease has led to numerous studies focused on potential new therapies, including molecules with antioxidant properties, [10][11][12] metabolites designed to boost mitochondrial oxidative phosphorylation function 13,14 or molecules that protect mitochondrial inner membrane phospholipids. [15][16][17] As substrate availability in the form of deoxyribonucleotide triphosphates (dNTPs) is vital to sustain mtDNA replication, administration of dNTPs or their precursors, deoxyribonucleosides (dNs), has been shown to increase mtDNA copy number in a range of different cell types in vitro. [18][19][20][21] Supplementation of dNs has also been used therapeutically to increase mtDNA copy number in patients with mitochondrial thymidine kinase 2 (TK2) deficiency, where they bypass the nucleotide generation defect in these patients.…”

Section: Introductionmentioning

confidence: 99%

Deoxyribonucleoside treatment rescues EtBr‐induced mtDNA depletion in iPSC‐derived neural stem cells with POLG mutations

et al. 2023

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Mutations in POLG, the gene encoding the catalytic subunit of the mitochondrial DNA (mtDNA) polymerase gamma (Pol‐γ), lead to diseases driven by defective mtDNA maintenance. Despite being the most prevalent cause of mitochondrial disease, treatments for POLG‐related disorders remain elusive. In this study, we used POLG patient‐induced pluripotent stem cell (iPSC)‐derived neural stem cells (iNSCs), one homozygous for the POLG mutation c.2243G>C and one compound heterozygous with c.2243G>C and c.1399G>A, and treated these iNSCs with ethidium bromide (EtBr) to study the rate of depletion and repopulation of mtDNA. In addition, we investigated the effect of deoxyribonucleoside (dNs) supplementation on mtDNA maintenance during EtBr treatment and post‐treatment repopulation in the same cells. EtBr‐induced mtDNA depletion occurred at a similar rate in both patient and control iNSCs, however, restoration of mtDNA levels was significantly delayed in iNSCs carrying the compound heterozygous POLG mutations. In contrast, iNSC with the homozygous POLG mutation recovered their mtDNA at a rate similar to controls. When we treated cells with dNs, we found that this reduced EtBr‐induced mtDNA depletion and significantly increased repopulation rates in both patient iNSCs. These observations are consistent with the hypothesis that mutations in POLG impair mtDNA repopulation also within intact neural lineage cells and suggest that those with compound heterozygous mutation have a more severe defect of mtDNA synthesis. Our findings further highlight the potential for dNs to improve mtDNA replication in the presence of POLG mutations, suggesting that this may offer a new therapeutic modality for mitochondrial diseases caused by disturbed mtDNA homeostasis.

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Recent advances in mitochondrial diseases: From molecular insights to therapeutic perspectives

Cited by 11 publications

References 186 publications

Nanomaterials in the Wound Healing Process: New Insights and Advancements

Nanomaterials in the Wound Healing Process: New Insights and Advancements

Caso de curso letal de mutación homocigota del gen nuclear mitocondrial hidroxiisobutiril-CoA hidrolasa HIBCH

Deoxyribonucleoside treatment rescues EtBr‐induced mtDNA depletion in iPSC‐derived neural stem cells with POLG mutations

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