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Mitochondria–cGAS–STING axis is a potential therapeutic target for senescence-dependent inflammaging-associated neurodegeneration

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Neural Regeneration Research 2025年第3期20卷 805-807页

作者： JoséM.Izquierdo centro de Biología Molecular Severo Ochoa(CBM) Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid(CSIC-UAM)MadridSpain

The word “senescence” comes from the Latin senescens, meaning “to begin to age”, and is characterized by a long-lasting but reversible block in proliferation, resulting from stress-induced cell cycle arrest of pre... 详细信息

关键词： Latin potential lasting

From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

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Neural Regeneration Research 2025年第3期20卷 660-670页

作者： Ernesto Doncel-Pérez Gabriel Guízar-Sahagún Israel Grijalva-Otero Hospital Nacional de Parapléjicos de Toledo Servicio de Salud de Castilla La Mancha(SESCAM)ToledoSpain Medical Research Unit for Neurological Diseases UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIIMSSCiudad de MéxicoMéxico

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoratio

关键词： neural regeneration neuroprotection spinal cord injury repair spinal cord injury treatments structural restoration of spinal cord injury

Precision medicine in pantothenate kinase-associated neurodegeneration

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Neural Regeneration Research 2019年第7期14卷 1177-1185页

作者： Mónica álvarez-Córdoba Marina Villanueva-Paz Irene Villalón-García Suleva Povea-Cabello Juan M.Suárez-Rivero Marta Talaverón-Rey Javier Abril-Jaramillo Ana Belén Vintimilla-Tosi José A.Sánchez-Alcázar centro Andaluz de Biología del desarrollo(CABD-CSIC-Universidad Pablo de Olavide) and Centro de Investigación Biomédica en Red:Enfermedades RarasInstituto de Salud Carlos Ⅲ centro de Neurología Avanzada centro Civet

Neurodegeneration with brain iron accumulation is a broad term that describes a heterogeneous group of progressive and invalidating neurologic disorders in which iron deposits in certain brain areas,mainly the basal *** predominant clinical symptoms include spasticity,progressive dystonia,Parkinson's disease-like symptoms,neuropsychiatric alterations,and retinal *** the neurodegeneration with brain iron accumulation disorders,the most frequent subtype is pantothenate kinase-associated neurodegeneration(PKAN) caused by defects in the gene encoding the enzyme pantothenate kinase 2(PANK2)which catalyzed the first reaction of the coenzyme A biosynthesis *** there is no effective treatment to prevent the inexorable course of these *** aim of this review is to open up a discussion on the utility of using cellular models derived from patients as a valuable tool for the development of precision medicine in ***,we have described that dermal fibroblasts obtained from PKAN patients can manifest the main pathological changes of the disease such as intracellular iron accumulation accompanied by large amounts of lipofuscin granules,mitochondrial dysfunction and a pronounced increase of markers of oxidative *** addition,PKAN fibroblasts showed a morphological senescence-like ***,pantothenate supplementation,the substrate of the PANK2 enzyme,corrected all pathophysiological alterations in responder PKAN fibroblasts with low/residual PANK2 enzyme ***,pantothenate treatment had no favourable effect on PKAN fibroblasts harbouring mutations associated with the expression of a truncated/incomplete *** correction of pathological alterations by pantothenate in individual mutations was also verified in induced neurons obtained by direct reprograming of PKAN *** observations indicate that pantothenate supplementation can increase/stabilize the expression levels of PANK2 in s

关键词： neurodegeneration with brain iron accumulation pantothenate kinase-associated neurodegeneration pantothenate kinase 2 pantothenate induced neurons precision medicine induced neuron fibroblast

Vicious cycle of lipid peroxidation and iron accumulation in neurodegeneration

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Neural Regeneration Research 2023年第6期18卷 1196-1202页

作者： Instituto de Salud Carlos III Irene Villalón-García Suleva Povea-Cabello MónicaÁlvarez-Córdoba Marta Talaverón-Rey Juan MSuárez-Rivero Alejandra Suárez-Carrillo Manuel Munuera-Cabeza Diana Reche-López Paula Cilleros-Holgado Rocío Piñero-Pérez JoséA.Sánchez-Alcázar centro Andaluz de Biología del desarrollo(CABD-CSIC-Universidad Pablo de Olavide de Sevilla) and Centro de Investigación Biomédica en Red:Enfermedades RarasInstituto de Salud Carlos IIISevillaSpain

Lipid peroxidation and iron accumulation are closely associated with neurodegenerative diseases,such as Alzheimer’s,Parkinson’s,and Huntington’s diseases,or neurodegeneration with brain iron accumulation *** dysfunction,lipofuscin accumulation,autophagy disruption,and ferroptosis have been implicated as the critical pathomechanisms of lipid peroxidation and iron accumulation in these ***,the connection between lipid peroxidation and iron accumulation and the initial cause or consequence in neurodegeneration processes is *** this review,we have compiled the known mechanisms by which lipid peroxidation triggers iron accumulation and lipofuscin formation,and the effect of iron overload on lipid peroxidation and cellular *** vicious cycle established between both pathological alterations may lead to the development of ***,the investigation of these mechanisms is essential for exploring therapeutic strategies to restrict *** addition,we discuss the interplay between lipid peroxidation and iron accumulation in neurodegeneration,particularly in PLA2G6-associated neurodegeneration,a rare neurodegenerative disease with autosomal recessive inheritance,which belongs to the group of neurodegeneration with brain iron accumulation disorders.

关键词： 4-hidroxynonenal ferroptosis iron lipid peroxidation lipofuscin neurodegeneration neurodegeneration with brain iron accumulation oxidative stress PLA2G6-associated neurodegeneration

Lanthanum-exchanged zeolite and clay as anticorrosive pigments for galvanized steel

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Journal of Rare Earths 2014年第4期32卷 352-359页

作者： S.Roselli N.Bellotti C.deyá M.Revuelta B.del Amo R.Romagnoli CIdePINT(centro de Investigación y desarrollo en tecnología de Pinturas)(CONICET-CIC)

A wide variety of inhibitive pigments is now being offered as possible alternatives to chromate and lead compounds for painted metals protection. Unfortunately, the most wide spread of these substitute pigments, zinc phosphate, has, at present, raised some environmental concern because phosphate causes the eutrophication of water courses and zinc itself is toxic. The aim of this re-search was to study the anticorrosive performance of a mixture consisting of zinc phosphate, modified zeolite and clay （bentonite） in order to diminish phosphate content in paints. The zeolite and the clay were exchanged with La（III） ions, as inorganic green inhibitor. In the first step, the anticorrosion protection by La（III） ions in solution was assessed by electrochemical tests. In the second step, an epoxy-polyamide paint formulated with the pigment mixture applied on galvanized panels was studied by salt spray test and electro-chemical noise measurements （ENM）. The results showed that it was possible to replace part of the zinc phosphate content in the paint with the exchanged zeolite and the clay.

关键词： exchanged pigments corrosion anticorrosive paints electrochemical noise measurements rare earths

Liver disease and erythropoietic protoporphyria:A concise review

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World Journal of Gastroenterology 2010年第36期16卷 4526-4531页

作者： María José Casanova-González María Trapero-Marugán E Anthony Jones Ricardo Moreno-Otero department of the Gastroenterology and Hepatology Hospital Universitario de la Princesa and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBEREHD)Madrid 28006Spain

The porphyries are a group of metabolic disorders characterized by deficiencies in the activity of enzymes involved in the biosynthesis of *** erythropoietic protoporphyria(EPP),in the majority of cases an autosomal dominant disease,there is a mutation of the gene that encodes ferrochelatase(FECH).FECH deficiency is associated with increased concentrations of protoporphyrin in erythrocytes,plasma,skin and *** prevalence of this inherited disorder oscillates between 1:75 000 and 1:200 *** manifestations of EPP appear in early infancy upon first exposure to the ***,approximately 5%-20% of patients with EPP develop liver *** of protoporphyrin in the liver is associated with cholestatic phenomena and oxidative stress that predisposes to hepatobiliary disease of varying degrees of severity,such as cholelithiasis,mild parenchymal liver disease,progressive hepatocellular disease with end-stage liver disease and acute liver *** damage is the major risk in EPP patients,so surveillance and frequent clinical and biochemical liver follow-up is *** diagnostic approach consists in detecting increased levels of protoporphyrin,decreased activity of FECH and genetic analysis of the FECH gene.A variety of nonsurgical therapeutic approaches have been adopted for the management of EPP associated with liver disease,but none of these has been shown to be unequivocally ***,some may have a place in preparing patients for liver *** transplantation does not correct the constitutional deficiency of ***,there is a risk of recurrence of liver disease after liver transplantation as a result of continuing overproduction of *** authors recommend that bone marrow transplantation should be considered in liver allograft recipients to prevent recurrence of hepatic disease.

关键词： Erythropoietic protoporphyria Protoporphyrin Liver Ferrochelatase

Immunogenetic biomarkers in inflammatory bowel diseases:Role of the IBD3 region

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World Journal of Gastroenterology 2014年第41期20卷 15037-15048页

作者： Manuel Muro Ruth López-Hernández Anna Mrowiec centro de Investigación biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd) Immunology ServiceUniversity Hospital Virgen de la Arrixaca

Many studies have demonstrated the linkage between the IBD3 region (6p21.1-23), an area which encompasses the famous human leukocyte antigen (HLA) complex, and Crohn’s disease (CD) or ulcerative colitis (UC). IBD3 is the only region that meets genome-wide significance, and provides stronger evidence of the linkage than 16p13.1-16q12.2 (IBD1), the locus that contains the susceptibility gene CARD15. However, despite these findings, IBD3 susceptibility genes remain elusive and unclear due to the strong linkage disequilibrium, extensive polymorphism, and high gene density that characterize this area and also due to varying allele frequencies in populations around the world. This area presents an extremely high abundance of genes, including the classical and non-classical major histocompatibility complex (MHC) class I and II genes, and other genes, namely MHC class III genes tumor necrosis factor (TNF)-α and -β, and Hsp, whose proteins play key functions in immunological processes. To date, it is not clear which genes within the MHC family contribute to the IBD pathogenesis, although certain HLA alleles have been associated with IBD. Recent insights into the biological function of other genes encoded within the IBD3 region, such as the MHC class I chain-related (MIC) genes, have led investigators to a more comprehensive exploration of this region. MHC class I chain-related molecule A (MICA) is highly polymorphic and interacts with NKG2D, its receptor on the surface of NK, Tγδ and T CD8+ cells. Increased expression of MICA in intestinal epithelial cells and increased expression of NKG2D in CD4+ T cells (lamina propria) in patients with CD have also been reported. MICA alleles have also been associated with IBD, and a variation at amino acid position 129 of the α2-heavy chain domain seems to categorize MICA alleles into strong and weak binders of NKG2D rece

关键词： IBD3 Tumor necrosis factor MICA HLA Inflammatory bowel disease

Misfolded amyloid-beta conformational variants(strains)as drivers of Alzheimer's disease neuropathology

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Neural Regeneration Research 2025年第11期20卷 3219-3220页

作者： Salvatore Saieva Rodrigo Morales department of Neurology The University of Texas Health Science Center at HoustonHoustonTXUSA centro Integrativo de Biologia y Quimica Aplicada(CIBQA) Universidad Bernardo O’HigginsSantiagoChile

Pathological and clinical variability in Alzheimer's disease(AD):AD is clinically cha racterized by progressive memory loss and cognitive *** a pathological point of view,the main features of AD are the deposition of amyloid plaques(composed of amyloid-beta,Aβ)and neurofibrillary tangles containing hyperphosphorylated Tau in the brain,accompanied by neu ronal and synaptic loss,neuroinflammation and brain atrophy(Jellinger,2022).Regardless of these common traits,growing evidence shows increased heterogen eity in the brain of AD patients considering both clinical manifestations and pathological features.

关键词： amyloid Alzheimer clinical

Role of peripheral amyloid-β aggregates in Alzheimer’s disease: mechanistic, diagnostic, and therapeutic implications

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Neural Regeneration Research 2025年第4期20卷 1087-1089页

作者： Nazaret Gamez Rodrigo Morales department of Neurology The University of Texas Health Science Center at HoustonHoustonTXUSA centro Integrativo de Biologia y Quimica Aplicada(CIBQA) Universidad Bernardo O’HigginsSantiagoChile

Compelling evidence demonstrates that the levels of peripheral amyloid-β(Aβ)fluctuate in Alzheimer’s disease(AD)***,Aβdeposits have been identified in peripheral ***,the relevance of peripheral Aβ(misfolded or not)in pathological situations,and the temporal appearance of these pathological fluctuations,are not well *** presence of misfolded Aβin peripheral compartments raises concerns on potential inter-individual transmissions considering the well-reported prion-like properties of this disease-associated *** latter is supported by multiple reports demonstrating that Aβmisfolding can be transmitted between humans and experimental animals through multiple routes of *** this mini-review,we discuss the potential implications of peripheral,disease-associated Aβin disease mechanisms,as well as in diagnostic and therapeutic approaches.

关键词： therapeutic amyloid latter