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Compartmentalized necroptosis activation in excitotoxicityinduced axonal degeneration: a novel mechanism implicated in neurodegenerative disease pathology

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Neural Regeneration Research 2019年第8期14卷 1385-1386页

作者： Macarena S. Arrazola Felipe A. Court center for Integrative Biology Faculty of Sciences Universidad Mayor de Chile Santiago CnileFONDAP Center for Geroscience Brain Health and Metabolism Santiago Chile Buck Institute for Research on Ageing Novato San Francisco CA USA

Excitotoxicity and neuronal cell death: Glutamate is the main excitatory neurotransmitter of the central nervous system and functionally involved in most brain activities, including brain development, synaptic plasticity, learning and memory. Exc让atory synaptic transmission is primarily mediated by ligana-gated ion channels, including a-amino-3-hydroxy-5-methylisoxazoIe-4-propionic acid (AMPA), N-methyl-D-aspartate (NMDA) and kainate receptors. Activation of glutamate receptors, particularly NMDA receptors, usually leads to calcium influx, whicn can act as a second messenger for several processes to mediate synaptic activity and brain function. Nevertheless, excessive release of glutamate neurotransmitter may produce intracellular calcium overload, leading to a cascade of events mediating cytoskeleton damage accompanied w让h reactive oxygen species (ROS) generation, mitochondrial dysfunction and ultimately neuronal cell death. These toxic effects of glutamate are known as excitotoxicity. Neuronal excitotoxicity has been linked to several acute and chronic brain diseases, such as stroke/ischemia, epilepsy and a range of neurodegenerative disorders, including Alzheimer's disease (AD), Huntingtons disease, amyotrophic lateral sclerosis (ALS) and Parkinsons disease (PD), contributing to the neuronal lost in different brain regions. Unfortunately, treating nervous system disorders with general glutamate receptor blockers has been associated with undesirable side effects, becoming increasingly necessary to unravel downstream effectors in the excitotoxicity-dependent cell death pathway in order to develop novel therapeutic strategies.

关键词： Compartmentalized necroptosis activation excitotoxicityinduced axonal neurodegenerative disease

Iron regulatory protein 1: the deadly switch of ferroptosis

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Neural Regeneration Research 2024年第3期19卷 477-478页

作者： Daniel A.Bórquez Pamela J.Urrutia center for Biomedical Research Faculty of MedicineUniversidad Diego PortalesSantiagoChile Institute of Nutrition&Food Technology(INTA) Universidad de ChileSantiagoChile geroscience center for Brain Health and Metabolism SantiagoChile

Ferroptosis,an iron-dependent cell death:Ferroptosis is a type of regulated necrosis,characterized by redox-active iron accumulation and increased free radical production derived by Fenton chemistry,that triggers oxidation of polyunsaturated fatty acids in phospholipids,loss of cellular membranes integrity,and leakage of intracellular contents.

关键词： integrity switch Iron

New insights on the molecular mechanisms of collateral sprouting after peripheral nerve injury

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Neural Regeneration Research 2021年第9期16卷 1760-1761页

作者： Dominique Lemaitre Felipe A.Court Universidad del Desarrollo Facultad de MedicinaCentro de Fisiología Celular e IntegrativaSantiagoChile center for Integrative Biology Faculty of SciencesUniversidad MayorSantiagoChile geroscience center for Brain Health and Metabolism(GERO) SantiagoChile The Buck Institute for Research on Aging NovatoCAUSA

Axonal regeneration after injuries to the nervous system has been extensively studied due to its implication in motor and sensory functional recovery. Distinct types of regeneration has been identified, such as canonical axonal regeneration, defined as the growth of axons from the transected axonal stump to reinnervate the original target, or regenerative sprouting, in which the growth occurs from a region of the damaged axon either close or far from the injury site(Tuszynski and Steward, 2012).

关键词： injuries injury collateral

Proapoptotic RECS1: a requisite gateway to lysosomal dysfunction and death

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Neural Regeneration Research 2022年第12期17卷 2695-2696页

作者： Philippe Pihán Mateus Milani Claudio Hetz Biomedical Neuroscience Institute Faculty of MedicineUniversity of ChileSantiagoChile center for geroscience Brain Health and Metabolism(GERO)SantiagoChile Program of Cellular and Molecular Biology Institute of Biomedical SciencesUniversity of ChileSantiagoChile Buck Institute for Research on Aging NovatoCAUSA

For a long time since their discovery by Christian de Duve in the 1950s,lysosomes have been referred to almost exclusively as passive garbage bags;the endpoint in the degradation of intra-and extracellular *** catabolic function of lysosomes is accomplished by an array of more than 60 acid hydrolases,which together break down a wide variety of biological macromolecules,including proteins,lipids,carbohydrates,and nucleic acids,for reutilization in the metabolic processes of the *** their optimal function,these enzymes require an acidic intraluminal pH of~4.5,which is maintained by the joint action of a proton pump,the vacuolar H+-ATPase,and several ion channels embedded in the lysosomal limiting membrane.

关键词： maintained limiting function

Therapeutic potential of insulin-like growth factor 2 in Huntington's disease: controlling proteostasis to alleviate the load of misfolded protein

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Neural Regeneration Research 2021年第8期16卷 1564-1565页

作者： Paulina Troncoso-Escudero Claudio Hetz Rene L.Vidal Biomedical Neuroscience Institute Faculty of MedicineUniversity of ChileSantiagoChile center for geroscience Brain Health and MetabolismSantiagoChile Program of Cellular and Molecular Biology Institute of Biomedical SciencesUniversity of ChileSantiagoChile center for Integrative Biology Faculty of SciencesUniversity MayorChile Buck Institute for Research on Aging NovatoCAUSA

Huntington's disease(HD) is an inherited autosomal dominant neurodegenerative disorder characterized by the development of adult-onset motor dysfunction,psychiatric disturbances and intellectual *** is associated with an expansion of CAG repeat sequence in the huntingtin gene(Htt).Exon 1 of Htt normally contains between 6 to 35 CAG repeats,whereas in patients affected with HD it contains more than 40 trinucleotides.

关键词： Huntington Therapeutic stasis

ERp57 in neurodegeneration and regeneration

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Neural Regeneration Research 2016年第2期11卷 232-233页

作者： Leslie Bargsted Claudio Hetz Soledad Matus Neurounion Biomedical Foundation CENPAR Santiago Chile Biomedical Neuroscience Institute Faculty of Medicine University of Chile Santiago Chile center for geroscience Brain Health and Metabolism Institute of Biomedical Sciences Center for Molecular Studies of the Cell Program of Cellular and Molecular Biology University of ChileSantiago Chile Department of Immunology and Infectious Diseases Harvard School of Public Health

The protein disulfide isomerases（PDIs）family has a central function in the folding of proteins synthetized through the secretory ***57,also known as Grp58 or PDIA3,is one of the main studied members of this family.

关键词： ERp57 in neurodegeneration and regeneration PDI

Commentary on"PANoptosis-like cell death in ischemia/reperfusion injury of retinal neurons"

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Neural Regeneration Research 2023年第2期18卷 341-341页

作者： Macarena S.Arrázola Felipe A.Court center for Integrative Biology Faculty of SciencesUniversidad Mayor geroscience center for Brain Health and Metabolism(GERO) SantiagoChile Buck Institute for Research on Aging NovatoCAUSA

See related article,pp 357-363Several decades have passed since programmedcell death(PCD)was *** was first defined by Kerr in 1972,and later described by the Nobel Prices in Physiology or Medicine 2002,Sydney Brenner,John Sulston and Robert Horwitz,who defined genetic regulators of apoptosis(Diamantis et al.,2008).However,it was in 1858 when the German pathologist and biologist Rudolf Virchow identified for the first time the phenomenon of apoptosis,which he named necrobiosis,arguing that this form of cell death was completely different from the uncontrolled necrosis,suggesting the existence of two different types of cell ***,the knowledge in the field of cell death regulation is extensive,but still under continuous expansion.

关键词： expansion death Sydney

Bursting the unfolded protein response accelerates axonal regeneration

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Neural Regeneration Research 2016年第6期11卷 892-893页

作者： Maritza Onate geroscience center for Brain Health and Metabolism Santiago Chile center for Integrative Biology Universidad Mayor Santiago Chile Biomedical Neuroscience Institute Faculty of Medicine University of Chile Santiago Chile Program of Cellular and Molecular Biology Institute of Biomedical Sciences Center for Molecular Studies of the Cell University of ChileSantiago Chile Millenium Nucleus for Regenerative Biology Santiago Chile Buck Institute for Research on Aging Novato CA 94945 USA Department of Immunology and Infectious Diseases Harvard School of Public Health Boston MA USA

Peripheral neuropathies refer to a group of conditions in which the peripheral nervous system(PNS)is *** pathological state are are associated with weakness,pain,and loss of motor and sensory *** than 100 types of peripheral neuropathies have been identified,with distinct symptoms and prognosis classified according to the type of damage to the *** to peripheral nerves results in disabling loss of sensory and motor func-

关键词： axonal regeneration sensory nerves prognosis weakness classified myelin glial neuronal

Preventing brain aging by the artificial enforcement of the unfolded protein response:future directions

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Neural Regeneration Research 2024年第2期19卷 393-394页

作者： Felipe Cabral-Miranda Claudio Hetz Instituto de Ciências Biomédicas Universidade Federal do Rio de JaneiroRio de JaneiroBrazil center for geroscience Brain Health and MetabolismSantiagoChile、Biomedical Neuroscience InstituteFaculty of MedicineUniversity of ChileSantiagoChile、Program of Cellular and Molecular BiologyInstitute of Biomedical SciencesFaculty of MedicineUniversity of ChileSantiagoChile、Buck Institute for Research on AgingNovatoCAUSA

As the life expectancy of the world’s population increases,age-related diseases are emerging as one of the greatest problems facing modern *** onset of dementia and neurodegenerative diseases is strictly dependent on aging as a major risk factor and has a profound impact on various aspects of the lives of individuals and their families.

关键词： diseases aging directions