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Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

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Neural Regeneration Research 2025年第3期20卷 725-739页

作者： Benjamin R.Helmold Angela Ahrens Zachary Fitzgerald P.Hande Ozdinler Department of Neurology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Center for Molecular Innovation and Drug Discovery Center for Developmental TherapeuticsChemistry of Life Processes InstituteNorthwestern UniversityEvanstonILUSA Mesulam Center for Cognitive Neurology and Alzheimer’s Disease Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Feinberg School of Medicine Les Turner ALS Center at Northwestern UniversityChicagoILUSA

Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.

关键词： als2 alsin amyotrophic lateral sclerosis hereditary spastic paraplegia neurodegenerative diseases personalized medicine precision medicine protein interactome protein-protein interactions SPAST spastin

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Current view and perspectives in amyotrophic lateral sclerosis

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Neural Regeneration Research 2017年第2期12卷 181-184页

作者： Stéphane Mathis Philippe Couratier Adrien Julian Philippe Corcia Gwendal Le Masson Department of Neurology Neuro-Muscular Unit and ALS Center CHU de Bordeaux (groupe hospitalier Pellegrin) Bordeaux cedex France Department of Neurology ALS Center Centre de competence SLA-federation Tours-Limoges CHU de Limoges Limoges France Department of Neurology CHU Poitiers University of Poitiers Poitiers France Department of Neurology ALS Center Centre de competence SLA-federation Tours-Limoges CHU de Tours Tours cedex 9 France

Amyotrophic lateral sclerosis（als）, identified as a distinct clinical entity by Charcot since the end of the nineteenth century, is a devastating and fatal neurodegenerative disorder that affects motor neurons in the brain, brainstem and spinal cord. Survival of patients with als is associated with several factors such as clinical phenotype, age at onset, gender, early presence of respiratory failure, weight loss and treatment with Riluzole（the only disease-modifying drug approved for this disease）. Nowadays, there is still no curative treatment for als： palliative care and symptomatic treatment are therefore essential components in the management of these patients. Nevertheless, the scientific knowledge in the field of als motor neuron degeneration is growing, with the prospect of new treatments. Based on this physiopathological knowledge, several new therapeutic targets are being studied, involving various mechanisms such as excitotoxicity, neuroinflammation, mitochondrial dysfunction, oxidative stress, RNA metabolism and other attractive concepts. Moreover, it is also important to identify reliable biomarkers that will be essential components for future therapeutic development and study design in als. In this review, we present the main recent advances and promising therapeutics and biomarkers in the field of als.

关键词： amyotrophic lateral sclerosis Charcot biomarkers research motor neuron neurodegeneration

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Safety and efficacy of ultrasound ciliary plasty as a primary intervention in glaucoma patients

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International Journal of Ophthalmology(English edition) 2019年第4期12卷 597-602页

作者： Magda A.Torky Yousif A Al Zafiri Sherein M.Hagras Abeer M.Khattab Rania M.Bassiouny Tharwat H.Mokbel Department of Ophthalmology Faculty of Medicine Mansoura University Department of Ophthalmology Dar AlS hifa Hospital

AIM: To evaluate the safety and the efficacy of the ultrasound ciliary plasty(UCP) on the intraocular pressure(IOP) control in glaucomatous eyes without previous glaucoma ***: A retrospective study included patients with primary and secondary glaucoma who underwent UCP in Dar Al Shifa Hospital, Kuwait between January 2017 to June 2018. High-intensity focused ultrasound procedures were performed under peribulbar anesthesia using the 2^(nd) generation probe with 8 s duration of each of the 6 shots. Complete ophthalmologic examinations were scheduled pre-treatment, and at 1 d, 1 wk, 1, 3, 6 and 12 mo posttreatment. Primary outcomes were the IOP reduction and success rates at 12 mo, while the secondary outcomes were the occurrence of vision threatening complications and visual ***: The records of 62 eyes of 62 patients were analyzed with mean age of 63.8 y(67.7% males). There was statistically significant reduction in the mean IOP from 35.2±8.3 mm Hg before treatment to 20.6±8.7 mm Hg at 12^(th) month(P<0.0005) with a mean percentage IOP reduction of 42.3% with significant reduction in the mean number of antiglaucomatous drugs from 3.2±0.4 before treatment to 2.1±1.02 at 12 mo(P<0.0005). Qualified success was achieved in 77.4% of eyes at 12 mo. No major intra-or posttreatment complications were ***: Second-generation UCP prove to be effective in reducing IOP in naive glaucoma patients with lower success rates in cases of neovascular and uveitic glaucomas.

关键词： ultrasound ciliary plasty glaucoma intraocular pressure

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High thermal stability and quantum yields of green-emitting Sr_3Gd_2(Si_3O_9)_2:Tb^(3+) phosphor by co-doping Ce^(3+)

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Journal of Rare Earths 2017年第1期35卷 41-46页

作者： ZHU Yingli LIANG Yujun LIU Shiqi LI Kai WU Xingya XU Rui Engineering Research Center of Nano-Geomaterials of Ministry of Education China University of Geosciences Wuhan 430074 China Faculty of Materi- als Science and Chemistry China University of Geoscienees Wuhan 430074 China

A series of Tb^3＋ mono-doped and Ce^3＋-Tb^3＋ co-doped Sr3Gd2（Si3O9）2 phosphors with high thermal stability and quantum yields were successfully prepared via the solid state reaction. The as-prepared Sr3Gd2（Si3O9）2：Tb^3＋ samples showed broad excitation spectrum from 250 to 400 nm and presented characteristic emission transitions ^5D4→^7FJ（J=6, 5, 4, 3） of Tb^3＋ under 313 nm excitation, which were located at about 488, 541, 584 and 620 nm. The emission intensities of Tb^3＋ rose steadily in Sr3Gd2（Si3O9）2 host with the increase of Tb^3＋ concentration even though Gd^3＋ ions were completely replaced by Tb^3＋ ions. The Ce^3＋ ion as a sensitizer could efficiently improve the performance of Tb^3＋ ion. First, with Ce^3＋ co-doping, the excitation spectrum of Tb^3＋ monitored at 541 nm showed a similar band that responds to the violet emission of Ce^3＋ monitored at 416 nm. Second, the quantum yields of Sr3Gd2（Si3O9）2：Tb^3＋ phosphors could be enhanced from 26.6% to 80.2% by co-doping Ce^3＋. Finally, the co-doping of Ce^3＋ was also effective to improve the thermal stability of Sr3Gd2（Si3O9）2：Tb^3＋. As the temperature rose to 150 oC, the emission intensity of Tb^3＋ remained at about 83.6% of that measured at room temperature, which was better than the commercial YAG：Ce phosphor in terms of their thermal quenching properties. These results indicated that the as-prepared Sr3Gd2（Si3O9）2：Tb^3＋,Ce^3＋ samples could be used as green emission phosphors for possible applications in near ultraviolet based WLEDs.

关键词： Sr3Gd2(Si3O9)2 photoluminescence quantum yields thermal stability luminescence rare earths

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Preparation of CuS-P（NIPAM-co-MAA） Hybrid Microgels with Controlled Surface Structures

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Chinese Journal of Chemistry 2011年第1期29卷 33-40页

作者： Zhang, Ying Liu, Huijin Fang, Yu Key Laboratory of Applied Surface and Colloid Chemistry Ministry of Education School of Chemistry and Materi- als Science Shaanxi Normal University Xi' an Shaanxi 710062 China

Copper sulfide-poly（isopropylacrylamide-co-methacrylic acid） [CuS-P（NIPAM-co-MAA）] hybrid microgels with patterned surface structures have been synthesized by means of the polymer microgel template technique. The results showed that the surface morphology of the hybrid microgels could be regulated by controlling the decomposition of thioacetamide （TAA） in an acidic medium. The rate of precipitation and the amount of metal sulfide significantly affect the surface structures of the hybrid microgels.

关键词： polymer microgels templates metal sulfides organic-inorganic hybrid composite

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Type XIX collagen: a promising biomarker from the basement membranes

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Neural Regeneration Research 2020年第6期15卷 988-995页

作者： Ana C.Calvo Laura Moreno Leticia Moreno Janne M.Toivonen Raquel Manzano Nora Molina Miriam de la Torre Tresa López Francisco J.Miana-Mena María J.Munoz Pilar Zaragoza Pilar Larrodé Alberto García-Redondo Rosario Osta Laboratory of Genetics and Biochemistry(LAGENBIO) University of ZaragozaFaculty of Veterinary SciencesInstituto de Investigación Sanitaria de Aragón(IIS)IA2CIBERNEDZaragozaSpain Hospital Clínico Universitario Lozano Blesa ZaragozaSpain Neurology Department ALS UnitCIBERER U-723Health Research InstituteMadridSpain

Among collagen members in the collagen superfamily,type XIX collagen has raised increasing interest in relation to its structural and biological *** XIX collagen is a Fibril-Associated Collagen with Interrupted Triple helices member,one main subclass of collagens in this *** collagen contains a triple helix composed of three polypeptide segments aligned in parallel and it is associated with the basement membrane zone in different *** molecular structure of type XIX collagen consists of five collagenous domains,COL1 to COL5,interrupted by six non-collagenous domains,NCI to *** most relevant domain by which this collagen exerts its biological roles is NCI domain that can be cleavage enzymatically to release matricryptins,exerting anti-tumor and anti-angiogenic effect in murine and human models of *** physiological conditions,type XIX collagen expression decreases after birth in different tissues although it is necessary to keep its basal levels,mainly in skeletal muscle and hippocampal and telencephalic interneurons in ***,in amyotrophic lateral sclerosis,altered transcript expression levels show a novel biological effect of this collagen beyond its structural role in basement membranes and its anti-tumor and anti-angiogenic *** XIX collagen can exert a compensatory effect to ameliorate the disease progression under neurodegenerative conditions specific to amyotrophic lateral sclerosis in transgenic SOD1 G93 A mice and amyotrophic lateral sclerosis *** novel biological role highlights its nature as prognostic biomarker of disease progression in and as promising therapeutic target,paving the way to a more precise prognosis of amyotrophic lateral sclerosis.

关键词： anti-tumor and anti-angiogenic properties C1 domain COL19A1 gene and protein levels compensatory effect FACIT collagens hippocampal interneurons matricryptins multiplexins NC1 domain regenerative response skeletal muscle type XIX collagen

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A Continuous Action Space Tree search for INverse desiGn (CASTING) framework for materials discovery

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npj Computational Materials 2023年第1期9卷 500-515页

作者： Suvo Banik Troy Loefller Sukriti Manna Henry Chan Srilok Srinivasan Pierre Darancet Alexander Hexemer Subramanian K.R.S.Sankaranarayanan Center for Nanoscale Materials Argonne National LaboratoryLemontIL 60439USA Department of Mechanical and Industrial Engineering University of IllinoisChicagoIL 60607USA Advanced Light Source(als)Division Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA

Material properties share an intrinsic relationship with their structural attributes,making inverse design approaches crucial for discovering new materials with desired *** Learning(RL)approaches are emerging as powerful inverse design tools,often functioning in discrete action *** constrains their application in materials design problems,which involve continuous search ***,we introduce an RL-based framework CASTING(Continuous Action Space Tree Search for inverse design),that employs a decision tree-based Monte Carlo Tree Search(MCTS)algorithm with continuous space adaptation through modified policies and *** representative examples like Silver(Ag)for metals,Carbon(C)for covalent systems,and multicomponent systems such as graphane,boron nitride,and complex correlated oxides,we showcase its accuracy,convergence speed,and scalability in materials discovery and ***,with the inverse design of super-hard Carbon phases,we demonstrate CASTING’s utility in discovering metastable phases tailored to user-defined target properties and preferences.

关键词： Action framework Tree

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Multifaceted superoxide dismutase 1 expression in amyotrophic lateral sclerosis patients:a rare occurrence?

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Neural Regeneration Research 2025年第1期20卷 130-138页

作者： Ilaria Martinelli Jessica Mandrioli Andrea Ghezzi Elisabetta Zucchi Giulia Gianferrari Cecilia Simonini Francesco Cavallieri Franco Valzania Department of Neurosciences Azienda Ospedaliero Universitaria di ModenaModenaItaly Clinical and Experimental Medicine Ph.D.Program University of Modena and Reggio EmiliaModenaItaly Department of Biomedical Metabolic and Neural SciencesUniversity of Modena and Reggio EmiliaModenaItaly Neurology unit Neuromotor&Rehabilitation DepartmentAzienda USL-IRCCS di Reggio EmiliaReggio EmiliaItaly

Amyotrophic lateral sclerosis(als)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal *** the typical clinical phenotype of als involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of *** superoxide dismutase 1(SOD1)mutations represent a minority of als cases,the SOD1 gene remains a milestone in als research as it represents the first genetic target for personalized *** numerous single case reports or case series exhibiting extramotor symptoms in patients with als mutations in SOD1(SOD1-als),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this *** this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during *** multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-als.

关键词： amyotrophic lateral sclerosis(als) autonomic extramotor genotype-phenotype multisystem involvement Parkinson’s disease sensory SOD1 superoxide dismutase 1 urinary vocal cord palsy

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Doubled Haploid Production Using an Improved Anther Culture Protocol for Sorghum[Sorghum bicolor(L.)Moench]

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Phyton-International Journal of Experimental Botany 2021年第2期90卷 475-487页

作者： Paul Chege Erzsébet Kiss Csaba Lantos Andrea Palágyi János Pauk Cereal Research Non-profit Ltd. Alsókikötősor 9Szeged6726Hungary Doctoral School of Plant Science Szent István UniversityGödöllőH2103Hungary

Sorghum[Sorghum bicolor(L.)Moench]can benefit from accelerated breeding and release of improved varieties through doubled haploid *** technology has been used in speeding up the breeding of other major cereals such as wheat,maize and rice,for which generally widely applied optimised protocols exist.A reproducible protocol for the crop,that can overcome genotype dependency and other species-specific challenges such as phenolic exudation is however *** study aimed at sorghum doubled haploids production thereby contributing to the development of an improved *** the 28 hybrid genotypes,both F1 registered-and experimental hybrids involved,this study successfully produced haploids from five genotypes and subsequently,four confirmed doubled-haploid lines on W14mf medium or its modification with 1.0 gl^(-1)L-proline,1.0 gl^(-1)L-asparagine and 1.0 gl^(-1)KH_(2)PO_(4).Medium 190-2Cu was used for regeneration and rooting,which occurred successfully,if the calli were transferred on to it less than 7 days after induction,and temperature was maintained at 25°C under light *** dependency was not wholly overcome;however,sorghum’s high tillering ability and abiotic stress tolerance were observed to contribute to attainment of haploid *** diploids producing seeds at rates of upto 80.5%were obtained,therefore eliminating the need for colchicine duplication.

关键词： In vitro androgenesis doubled-haploid sorghum anther-culture breeding

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Efficacy of glucagon-like peptide-1 mimetics for neural regeneration

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Neural Regeneration Research 2015年第11期10卷 1723-1724页

作者： Kazunori Sango Kazunori Utsunomiya Diabetic Neuropathy Project (Former als/Neuropathy project) Department of Sensory and Motor Systems Tokyo Metropolitan Institute of Medical Science Division of Diabetes Metabolism & Endocrinology Department of Internal Medicine Jikei University School of Medicine

Glucagon-like peptide 1（GLP-1）is secreted from enteroendocrine L cells in response to nutrient ingestion and exhibits insulinotropic properties by stimulating specific G protein-linked receptors（GLP-1Rs）on pancreaticβ*** GLP-1 mimetics,such as exenatide（exendin-4（Ex-4））,liraglutide,and lixisenatide,have been developed and approved as treatments for patients with type 2 *** peptides show bioactiv-ities almost identical to those of GLP- 1 and have a substantially longer plasma half-life than GLP-1 because of their resistance to dipeptidyl peptidase-4, a GLP-1 degrading enzyme.

关键词： GLP DRG Efficacy of glucagon-like peptide-1 mimetics for neural regeneration

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