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The big data challenge-and how polypharmacology supports the translation from pre-clinical research into clinical use against neurodegenerative diseases and beyond

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Neural Regeneration Research 2024年第8期19卷 1647-1648页

作者： Sven Marcel Stefan Muhammad Rafehi Drug Development and Chemical Biology Lübeck Institute of Experimental Dermatology(LIED)University of Lübeck and University Medical Center Schleswig-HolsteinLübeckGermany Department of Pathology Section of NeuropathologyTranslational Neurodegeneration Research and Neuropathology LabUniversity of Oslo and Oslo University HospitalOsloNorway School of Medical Sciences Faculty of Medicine and HealthUniversity of SydneySydneyNSWAustralia Institute of Clinical Pharmacology University Medical Center GöttingenGöttingenGermany Department of Medical Education Augsburg University MedicineAugsburgGermany

Introductory comments:The identification and validation of disease-modifying proteins are fundamental aspects in drug ***,the m ultifactority of n eurodegen era tive diseases poses a real challenge for targeted ***,the behavior of individually(over-)expressed to rget proteins in vitro is likely to differ from their actual functional behavior when embedded in cascades and pathways in vivo.

关键词： translation beyond likely

A lead role for a“secondary”axonal injury response

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Neural Regeneration Research 2025年第2期20卷 469-470页

作者： Melissa A.Rudy Trent A.Watkins Division of neuroimmunology and Glial Biology Department of NeurologyUniversity of California at San FranciscoSan FranciscoCAUSA Development Disease Modelsand Therapeutics Graduate ProgramBaylor College of MedicineHoustonTXUSA

Stress signaling following axon injury stimulates a transcriptional program for regeneration that might be exploited to promote central nervous system ***,this stress response drives neuronal apoptosis in non-regenerative *** duality presents a quandary for the development of therapeutic interventions:manipulating stress signaling to enhance recovery of damaged neurons risks accelerating neurodegeneration or restricting regenerative *** dichotomy is well illustrated by the fates of retinal ganglion cells(RGCs)following optic nerve *** this central nervous system injury model,disruption of a stress-activated MAP kinase(MAPK)cascade blocks the extensive apoptosis of RGCs that occurs in wild-type mice(Watkins et al.,2013;Welsbie et al.,2017).

关键词： injury axonal stress

Dental pulp stem cells, a paracrine-mediated therapy for the retina

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Neural Regeneration Research 2014年第6期9卷 577-578页

作者： Ben Mead Ann Logan Martin Berry Wendy Leadbeater Ben A. Scheven Neurotrauma and neurodegeneration section School of Clinical and Exper-imental Medicine University of Birmingham School of Dentistry University of Birmingham

Author contributions： Mead B was responsible for study conception and design, collection and^or assembly of data, data analysis and interpretation and manuscript writing. Logan A participated in study conception and design, data analysis and interpretation and manuscript writing. Berry M was responsible for manuscript writing. Scheven BA was in charge of study conception and design, data analysis and interpretation and manuscript writing. Leadbeater W participated in study conception and design, data analysis and interpretation and manuscript writing. All authors approved the final version of this paper.

关键词： stem cell DPSCs RGCs a paracrine-mediated therapy for the retina Dental pulp stem cells BMSCs

Promoting remyelination for the treatment of multiple sclerosis:opportunities and challenges

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Neuroscience Bulletin 2013年第2期29卷 144-154页

作者： Yueting Zhang Taylor B.Guo Hongtao Lu neuroimmunology Discovery Performance Unit GlaxoSmithKline Research and Development Center

Multiple sclerosis （MS） is a chronic and devastating autoimmune demyelinating disease of the central nervous system. With the increased understanding of the pathophysiology of this disease in the past two decades, many disease-modifying therapies that primarily target adaptive immunity have been shown to prevent exacerbations and new lesions in patients with relapsing-remitting MS. However, these therapies only have limited efficacy on the progression of disability. Increasing evidence has pointed to innate immunity, axonal damage and neuronal loss as important contributors to disease progression. Remyelination of denuded axons is considered an effective way to protect neurons from damage and to restore neuronal function. The identification of several key molecules and pathways controlling the differentiation of oligodendrocyte progenitor cells and myelination has yielded clues for the development of drug candidates that directly target remyelination and neuroprotection. The long-term efficacy of this strategy remains to be evaluated in clinical trials. Here, we provide an overview of current and emerging therapeutic concepts, with a focus on the opportunities and challenges for the remyelination approach to the treatment of MS.

关键词： multiple sclerosis myelination neurodegeneration oligodendrocytes disease progression disease modifying therapy drug target animal models

Trans-synaptic degeneration as a mechanism of neurodegeneration in multiple sclerosis

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Neural Regeneration Research 2023年第12期18卷 2682-2684页

作者： Olwen C.Murphy Peter A.Calabresi Shiv Saidha Division of neuroimmunology and Neurological Infections Department of NeurologyJohns Hopkins UniversityBaltimoreMDUSA

Multiple sclerosis(MS) is regarded as an immunemediated,demyelinating disorder of the central nervous system,however neuroaxonal degeneration is accepted as the principal substrate of disability accumulation(Dutta and... 详细信息

关键词： degeneration sclerosis myelin

Fused in sarcoma-amyotrophic lateral sclerosis as a novel member of DNA single strand break diseases with pure neurological phenotypes

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Neural Regeneration Research 2021年第1期16卷 110-112页

作者： Marcel Naumann Julian Laubenthal Andreas Hermann Translational neurodegeneration section“Albrecht-Kossel” Department of NeurologyUniversity Medical Center RostockUniversity of RostockRostockGermany German Center for Neurodegenerative Diseases(DZNE)Rostock/Greifswald Center for Transdisciplinary Neurosciences Rostock(CTNR)University Medical Center RostockUniversity of RostockRostockGermany

Accumulation of DNA damage and genomic instability are believed to have crucial effects in neurodegenerative conditions such as Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,premature aging diseases as well as amyotrophic lateral sclerosis(ALS)and frontotemporal dementia(FTD).Until recently these studies were largely correlative in nature,though raising the possibility that defects in the DNA damage response(DDR)underlie neurodegenerative diseases.

关键词： diseases Huntington amyotrophic

The expanding phenotype of stroke-induced immune alterations

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neuroimmunology and Neuroinflammation 2014年第1期1卷 15-16页

作者： Johanna Ruhnau Antje Vogelgesang Alexander Dressel Department of Neurology Neuroimmunology SectionUniversity Medicine Greifswald17489 GreifswaldGermany

INTRODUCTION The clinical outcome of ischemic stroke patients is determined by the extent of the ischemic lesion as well as the occurrence of severe systemic *** with pneumonia have a three-fold increase in 30-day mor... 详细信息

关键词： alterations clinical mortality

Combination of novel RNA sequencing and sophisticated network modeling to reveal a common denominator in amyotrophic lateral sclerosis?

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Neural Regeneration Research 2023年第11期18卷 2403-2405页

作者： Banaja P.Dash Andreas Hermann Translational neurodegeneration section“Albrecht Kossel” Department of NeurologyUniversity Medical Center RostockRostockGermany Center for Transdisciplinary Neurosciences Rostock University Medical Center RostockRostockGermany Deutsches Zentrum für Neurodegenerative Erkrankungen(DZNE)Rostock/Greifswald RostockGermany

Amyotrophic lateral sclerosis (ALS) is one of the most dreadful neurodegenerative diseases leading to death within 1-5 years after symptom *** majority of ALS cases are sporadic(sALS),while the remaining 5-10%are familial(fALS).Genetic discoveries have identified ALScausative mutations in more than 30 genes so far(Chia et al.,2018).Indeed,the four most common mutations observed in ALS genes in Europe are the hexanucleotide expansion repeat in Chromosome9 Open Reading Frame 72 (C9ORF72),Cu-Zn superoxide dismutase 1 (SOD1),tra nsactive response DNA Binding protein 43kDa (TARDBP)and fused in sa rcoma (FUS).

关键词： diseases death

Autophagy and neurodegenerative disorders

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Neural Regeneration Research 2013年第24期8卷 2275-2283页

作者： Evangelia Kesidou Roza Lagoudaki Olga Touloumi Kyriaki-Nefeli Poulatsidou Constantina Simeonidou Laboratory of Experimental Neurology and neuroimmunology Second Department of Neurology AHEPA University Hospital Aristotle University of Thessaloniki Department of Experimental Physiology Medical School Aristotle University of Thessaloniki

Accumulation of aberrant proteins and inclusion bodies are hallmarks in most neurodegenerative diseases. Consequently, these aggregates within neurons lead to toxic effects, overproduction of reactive oxygen species and oxidative stress. Autophagy is a significant intracellular mechanism that removes damaged organelles and misfolded proteins in order to maintain cell homeostasis. Excessive or insufficient autophagic activity in neurons leads to altered homeostasis and influences their survival rate, causing neurodegeneration. The review article provides an update of the role of autophagic process in representative chronic and acute neurodegenerative disorders.

关键词： neural regeneration reviews oxidative stress autophagy autophagy-related genes apoptosis Parkinson's disease amyotrophic lateral sclerosis multiple sclerosis acute and chronic neurode-generation neuroregeneration