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Beyond neurodegeneration:engineering amyloids for biocatalysis

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Neural Regeneration Research 2025年第10期20卷 2915-2916页

作者： Andrea Bartolomé-Nafría Javier García-Pardo salvador ventura Institut de Biotecnologia i de Biomedicina(IBB)and Departament de Bioquímica i Biologia Molecular Universitat Autònoma de BarcelonaBellaterraBarcelonaSpain Hospital Universitari Parc Taulí Institut d’Investigaciói InnovacióParc Taulí(I3PT-CERCA)Universitat Autònoma de BarcelonaSabadellSpain

Amyloid fibrils are highly organized protein or peptide aggregates,often characterized by a distinctive supramolecular cross-β-sheet *** formation and accumulation of these structures have been traditionally associated with neural or systemic human diseases,such as Alzheimer’s disease,Parkinson’s disease,type-2 diabetes,or amyotrophic lateral sclerosis(Wei et al.,2017;Wittung-Stafshede,2023).

关键词： structure amyloid

Prion-like domain disease-causing mutations and misregulation of alternative splicing relevance in limb-girdle muscular dystrophy (LGMD) 1G

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Neural Regeneration Research 2020年第12期15卷 2239-2240页

作者： Cristina Batlle salvador ventura Departament de Bioquímica i Biologia Molecular and Institut de Biotecnologia i Biomedicina Universitat Autònoma de BarcelonaBellaterraSpain

Human prion-like proteins often correspond to nucleic acid binding proteins,displaying both globular domains and long intrinsically disordered regions(IDRs)(Harrison and Shorter,2017).Their IDRs are of low complexity and resemble in amino acid composition to the disordered yeast prion domains,being usually enriched in Gln and Asn residues and depleted in hydrophobic and charged ***,these sequence stretches are named prion-like domains(PrLDs).Prion-like proteins can aggregate into amyloid fibrils,which can accommodate incoming protein monomers,propagating thus the polymeric fold,both processes being。

关键词： dystrophy muscular amyloid

One ring is sufficient to inhibit α-synuclein aggregation

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Neural Regeneration Research 2022年第3期17卷 508-511页

作者： Samuel Peña-Díaz salvador ventura Institut de Biotecnologia i Biomedicina Universitat Autònoma de BarcelonaBellaterraSpain Departament de Bioquímica i Biologia Molecular Universitat Autònoma de BarcelonaBellaterraSpain InstitucióCatalana de Recerca i Estudis Avançats(ICREA) BarcelonaSpain

Parkinson's disease,the second most prevalent neurodegenerative disorder worldwide,is characterized by a progressive loss of dopaminergic neurons in substantia nigra pars compacta,causing motor *** disorder's main hallmark is the formation of intraneuronal protein inclusions,named Lewy bodies and *** major component of these arrangements is α-synuclein,an intrinsically disordered and soluble protein that,in pathological conditions,can form toxic and cell-to-cell transmissible amyloid *** α-synuclein aggregation has attracted significant effort in the search for a disease-modifying therapy for Parkinson's *** molecules like Synu Clean-D,epigallocatechin gallate,trodusquemine,or anle138 b exemplify this therapeutic ***,we describe a subset of compounds containing a single aromatic ring,like dopamine,ZPDm,gallic acid,or entacapone,which act as molecular chaperones against α-synuclein *** simplicity of their structures contrasts with the complexity of the aggregation process,yet the block efficiently α-synuclein assembly into amyloid fibrils,in many cases,redirecting the reaction towards the formation of non-toxic off-pathway ***,some of these compounds can disentangle mature α-synuclein amyloid *** simple structures allow structure-activity relationship analysis to elucidate the role of different functional groups in the inhibition of α-synuclein aggregation and fibril dismantling,making them informative lead scaffolds for the rational development of efficient drugs.

关键词： amyloid aromatic rings dopamine inhibition neurodegeneration oligomers Parkinson's disease protein aggregation α-synuclein

Inducing α-synuclein compaction: a new strategy for inhibiting α-synuclein aggregation?

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Neural Regeneration Research 2019年第11期14卷 1897-1898页

作者： Francisca Pinheiro salvador ventura Institut de Biotecnologia i Biomedicina Universitat Autonoma de BarcelonaBellaterraSpainDepartament de Bioquimica i Biologia MolecularUniversitat Autonoma de BarcelonaBellaterraSpain

Proteins might misfold during translation and folding or even once they are in their native states, due to stochastic fluctuations, destabilizing mutations or cellular stress. Aberrant protein species are usually detected and either refolded or cleared by the protein quality control machinery (Ciechanover and Kwon, 2015). When misfolded protein conformers cannot be degraded, they tend to self-assemble to form aggregates, a characteristic of many neurodegenerative diseases.

关键词： inhibitingα-synuclein aggregation native states protein quality control machinery

LL-37 and CsgC exemplify the crosstalk between anti-amyloid, antimicrobial, and anti-biofilm protein activities

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Neural Regeneration Research 2023年第5期18卷 1027-1028页

作者： Jaime Santos salvador ventura Irantzu Pallares Institut de Biotecnologia i Biomedicina Departament de Bioquímica i Biologia Molecular Universitat Autònoma de Barcelona

Protein misfolding and aggregation into amyloid fibrils is the main pathological hallmark of neurodegenerative diseases,including Alzheimer’s,Parkinson’s,Huntington’s,and prion diseases(Chiti and Dobson,2017).These insoluble fibrillar deposits possess a common structure characterized by a cross-β-sheet conformation in which β-strands run transversely to the fiber axis and form an intermolecular network of hydrogen bonds.

关键词： amyloid Huntington diseases

Small molecules to prevent the neurodegeneration caused by α-synuclein aggregation

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Neural Regeneration Research 2020年第12期15卷 2260-2261页

作者： Samuel Pena-Díaz Jordi Pujols salvador ventura Institut de Biotecnologia i Biomedicina Departament de Bioquímica i Biologia MolecularUniversitat Autònoma de BarcelonaBellaterraSpain

Parkinson’s disease (PD) is a neurodegenerative disorder belonging to a group of human pathologies known as synucleinopathies,which includes multiple system atrophy or dementia with Lewy bodies (Spillantini et al.,1998).These diseases share a common neuropathological feature,the presence ofα-synuclein (α-Syn) deposits,although they differ in the cellular and anatomical compartment in whichα-Syn inclusions *** affects more than 1% of people over 60 years of age,thus being the second most prevalent neurodegenerative disease in the world and the most common synucleinopathy.

关键词： al. diseases atrophy

Small molecules to target tau amyloid aggregation

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Neural Regeneration Research 2024年第3期19卷 509-511页

作者： Zoe Manglano-Artuñedo Samuel Peña-Díaz salvador ventura Institut de Biotecnologia i Biomedicina Universitat Autònoma de BarcelonaBellaterraSpain

Protein aggregation has been linked with many neurodegenerative diseases,such as Alzheimer’s disease(AD)or Parkinson’s *** belongs to a group of heterogeneous and incurable neurodegenerative disorders collectively known as *** comprise frontotemporal dementia,Pick’s disease,or corticobasal degeneration,among *** symptomatology varies with the specific tau protein variant involved and the affected brain region or cell ***,they share a common neuropathological hallmark-the formation of proteinaceous deposits named neurofibrillary *** tangles,primarily composed of aggregated tau(Zhang et al.,2022),disrupt normal neuronal functions,leading to cell death and cognitive decline.

关键词： tau degeneration aggregation

Growth Hormone Prevents the Memory Deficit Caused by Oxidative Stress in Early Neurodegenerative Stage in Rats

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Neuroscience & Medicine 2012年第3期3卷 287-293页

作者： Diana Verónica Castillo-Padilla Gabino Borgornio-Pérez Alejandro Zentella-Dehesa Adrian Sandoval-Montiel José Luis ventura Gallegos Selva Rivas-Arancibia Facultad de Medicina Departamento de Fisiología Universidad Nacional Autónoma de México Ciudad Universitaria México Instituto de Investigaciones Biomédicas Universidad Nacional Autónoma de México Ciudad Universitaria México Unidad de Bioquímica Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Tlalpan México

Oxidative stress has been involved in neurodegenerative diseases. The growth hormone (GH) counteracts the levels of reactive oxygen species. Previously, we showed that the prolonged exposure to ozone causes oxidative stress in the hippocampus and memory deficits. In this work, we analyzed the effects of the growth hormone on the memory deficit generated by ozone exposure, growth hormone effects on the Insulin-like growth factor I (IGF-I), and the serinethreonine protein kinase (Akt) activation in the dentate gyrus. Our results show that GH prevents memory deficits in early stages of the neurodegenerative process.

关键词： Oxidative Stress Growth Hormone Insulin Growth Factor Ozone Serine-Threonine Protein Kinase Water Maze Passive Avoidance

Performance and calibration of quark/gluon-jet taggers using 140 fb^(-1) of pp collisions at √s=13 TeV with the ATLAS detector

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Chinese Physics C 2024年第2期48卷 1-25页

作者： G. Aad B. Abbott K. Abeling N.J. Abicht S.H. Abidi A. Aboulhorma H. Abramowicz H. Abreu Y. Abulaiti B.S. Acharya C. Adam Bourdarios L. Adamczyk S.V. Addepalli M.J. Addison J. Adelman A. Adiguzel T. Adye A.A. Affolder Y. Afik M.N. Agaras J. Agarwala A. Aggarwal C. Agheorghiesei A. Ahmad F. Ahmadov W.S. Ahmed S. Ahuja X. Ai G. Aielli A. Aikot M. Ait Tamlihat B. Aitbenchikh I. Aizenberg M. Akbiyik T.P.A. Åkesson A.V. Akimov D. Akiyama N.N. Akolkar K. Al Khoury G.L. Alberghi J. Albert P. Albicocco G.L. Albouy S. Alderweireldt M. Aleksa I.N. Aleksandrov C. Alexa T. Alexopoulos F. Alfonsi M. Algren M. Alhroob B. Ali H.M.J. Ali S. Ali S.W. Alibocus M. Aliev G. Alimonti W. Alkakhi C. Allaire B.M.M. Allbrooke J.F. Allen C.A. Allendes Flores P.P. Allport A. Aloisio F. Alonso C. Alpigiani M. Alvarez Estevez A. Alvarez Fernandez M. Alves Cardoso M.G. Alviggi M. Aly Y. Amaral Coutinho A. Ambler C. Amelung M. Amerl C.G. Ames D. Amidei S.P. Amor Dos Santos K.R. Amos V. Ananiev C. Anastopoulos T. Andeen J.K. Anders S.Y. Andrean A. Andreazza S. Angelidakis A. Angerami A.V. Anisenkov A. Annovi C. Antel M.T. Anthony E. Antipov M. Antonelli F. Anulli M. Aoki T. Aoki J.A. Aparisi Pozo M.A. Aparo L. Aperio Bella C. Appelt A. Apyan N. Aranzabal S.J. Arbiol Val C. Arcangeletti A.T.H. Arce E. Arena J-F. Arguin S. Argyropoulos J.-H. Arling O. Arnaez H. Arnold G. Artoni H. Asada K. Asai S. Asai N.A. Asbah J. Assahsah K. Assamagan R. Astalos S. Atashi R.J. Atkin M. Atkinson H. Atmani P.A. Atmasiddha K. Augsten S. Auricchio A.D. Auriol V.A. Austrup G. Avolio K. Axiotis G. Azuelos D. Babal H. Bachacou K. Bachas A. Bachiu F. Backman A. Badea P. Bagnaia M. Bahmani A.J. Bailey V.R. Bailey J.T. Baines L. Baines O.K. Baker E. Bakos D. Bakshi Gupta V. Balakrishnan R. Balasubramanian E.M. Baldin P. Balek E. Ballabene F. Balli L.M. Baltes W.K. Balunas J. Balz E. Banas M. Bandieramonte A. Bandyopadhyay S. Bansal L. Barak M. Barakat E.L. Barberio D. Barberis M. Barbero M.Z. Barel K.N. Barends T. Barillari M-S. Barisits T. Barklow P. Baron D.A. Baron Mo The ATLAS Collaboration

The identification of jets originating from quarks and gluons,often referred to as quark/gluon tagging,plays an important role in various analyses performed at the Large Hadron Collider,as Standard Model measurements and searches for new particles decaying to quarks often rely on suppressing a large gluon-induced *** paper describes the measurement of the efficiencies of quark/gluon taggers developed within the ATLAS Collaboration,using √s=13 TeV proton–proton collision data with an integrated luminosity of 140 fb^(-1) collected by the ATLAS *** taggers with high performances in rejecting jets from gluon over jets from quarks are studied:one tagger is based on requirements on the number of inner-detector tracks associated with the jet,and the other combines several jet substructure observables using a boosted decision tree.A method is established to determine the quark/gluon fraction in data,by using quark/gluon-enriched subsamples defined by the jet *** in tagging efficiency between data and simulation are provided for jets with transverse momentum between 500 GeV and 2 TeV and for multiple tagger working points.

关键词： ATLAS JET QUARK GLUON TAGGING