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Neural Regeneration Research 2016年第6期11卷 900-901页

作者： Eugenia Trushina department of Neurology Mayo Clinic department of Molecular Pharmacology and experimental therapeutics Mayo Clinic

Mitochondria,the powerhouses of the cell,are dynamic organelles that constantly move and change their size and morphology to meet energetic demands of the cell（Wai and Langer,2016）.Recent studies demonstrated that energy production is dependent on the ability of mitochondria to undergo cycles of fission and fusion collectively termed“mitochondrial dynamics”（Youle and van der Bliek,2012）.

关键词： mitochondrial phenotype Langer constantly fission hippocampal neuronal unusual protective deprivation

Nilotinib:from animal-based studies to clinical investigation in Alzheimer's disease patients

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Neural Regeneration Research 2023年第4期18卷 803-804页

作者： Annalisa Nobili Marcello D’Amelio Maria Teresa Viscomi department of Medicine and Surgery University Campus Bio-MedicoDepartment of Experimental NeuroscienceIRCCS Santa Lucia FoundationRomeItaly department of Life Science and Public Health Section of Histology and Embryology UniversitàCattolica del Sacro CuoreFondazione Policlinico Universitario“A.Gemelli”IRCCSRomeItaly

Since their first description in the brains of patients suffering from Alzheimer ’s disease(AD), more than 100 years ago, extracellular amyloid-β(Aβ) plaques and intracellular neurofibrillary tangles have been the principal focus of AD research. However, this focus has led to the failure of several long and promising clinical trials, and the efficacy of new Aβ-targeting drugs to slow down the disease progression is still controversial despite being successful in reducing the Aβ load.

关键词： Alzheimer Aβ drugs

Click chemistry and drug delivery:A bird's-eye view

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Acta Pharmaceutica Sinica B 2023年第5期13卷 1990-2016页

作者： Shameer M.Kondengadan Shubham Bansal Ce Yang Dongning Liu Zach Fultz Binghe Wang department of Chemistry and Center for Diagnostics and therapeutics Georgia State UniversityAtlantaGA 30303USA

Click chemistry has been proven to be very useful in drug *** to the availability of a large number of click reactions with a various characteristics,selection of appropriate chemistry for a given application is often not a trivial *** review is written for pharmaceutical researchers who are interested in click chemistry applications and yet may not be click chemistry *** this,the review gives an overview of available click reactions organized by application ***,the general understanding of click reactions being fast and high yielding sometimes overshadows the need to analyze reaction kinetics in assessing suitability of a given reaction for certain *** this,we highlight the need to analyze the relationship among reaction kinetics,concentration effects,and reaction time scales,knowing that lack of such analysis could easily lead to ***,possible issues such as chemical stability with various click reagents are also discussed to aid experimental *** examples and extensive references are also provided to aid in-depth understanding of technical *** hope this review will help those interested in using click chemistry in drug delivery to select the appropriate reactions/reagents and minimize the number of pitfalls.

关键词： Bioorthogonal chemistry Bond-breaking reaction PROTAC Antibody—drug conjugates Gasotransmitters

Next-Generation Tools to Study Autonomic Regulation In Vivo

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neuroscience Bulletin 2019年第1期35卷 113-123页

作者： Snigdha Mukerjee Eric Lazartigues department of Pharmacology and experimental therapeutics Louisiana State University Health Sciences Center neuroscience and Cardiovascular Centers of Excellence Louisiana State University Health Sciences Center Southeast Louisiana Veterans Health Care System

The recent development of tools to decipher the intricacies of neural networks has improved our understanding of brain function. Optogenetics allows one to assess the direct outcome of activating a geneticallydistinct population of neurons. Neurons are tagged with light-sensitive channels followed by photo-activation with an appropriate wavelength of light to functionally activate or silence them, resulting in quantifiable changes in the periphery. Capturing and manipulating activated neuron ensembles, is a recently-designed technique to permanently label activated neurons responsible for a physiological function and manipulate them. On the other hand, neurons can be transfected with genetically-encoded Ca2^+ indicators to capture the interplay between them that modulates autonomic end-points or somatic behavior. These techniques work with millisecond temporal precision. In addition, neurons can be manipulated chronically to simulate physiological aberrations by transfecting designer G-protein-coupled receptors exclusively activated by designer drugs. In this review, we elaborate on the fundamental concepts and applications of these techniques in research.

关键词： Autonomic regulation Optogenetics Calcium sensors DREADD

Early life stress-induced neuroinflammation and neurological disorders: a novel perspective for research

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Neural Regeneration Research 2022年第9期17卷 1971-1972页

作者： Clarissa Catale Valeria Carola Maria Teresa Viscomi Division of experimental neuroscience IRCCS Santa Lucia FoundationRomeItaly department of Dynamic and Clinical Psychology and Health StudiesSapienza University of RomeRomeItaly department of Life Science and Public Health Section of Histology and EmbryologyUniversitàCattolica del S.CuoreRomeItaly

Childhood maltreatment(CM)has been consistently linked with numerous detrimental outcomes concerning physical and psychological ***,few studies have explored vulnerability to neurological disorders after *** life adversity,in the form of poverty,stress and abuse,has been associated with decline in cognitive function and dementia later in life(Short and Baram,2019).Robust preclinical data suggest that early life stress(ELS)may increase the risk and worsen the course of neurological disorders such as Alzheimer’s(AD)and Parkinson’s(PD)diseases,and traumatic brain injury(TBI)(Lesuis et al.,2018;Short and Baram,2019;He et al.,2020;Catale et al.,2021;Sanchez et al.,2021).

关键词： neurological disorders inflammation

Metabotropic glutamate receptor 1 alpha:a unique receptor variant with variable implications for Alzheimer’s disease pathogenesis

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Neural Regeneration Research 2023年第10期18卷 2196-2197页

作者： Jason HY Yeung Andrea Kwakowsky Centre for Brain Research Department of Anatomy and Medical ImagingFaculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand Pharmacology and therapeutics School of MedicineGalway Neuroscience CentreOllscoil na Gaillimhe-University of GalwayGalwayIreland

Alzheimer’s disease (AD) is the leading neurodegenerative disorder *** this,there is minimal effective therapeutics proven to reduce or prevent the progression of this *** is the main excitatory neurotransmitter with... 详细信息

关键词： Alzheimer Metab pathogenesis

Is EAAT2 a potential therapeutic intervention target for Alzheimer's disease?

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Neural Regeneration Research 2023年第8期18卷 1721-1722页

作者： Oliver WG Wood Jason HY Yeung Andrea Kwakowsky Centre for Brain Research Department of Anatomy and Medical ImagingFaculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand Pharmacology and therapeutics School of MedicineGalway Neuroscience CentreOllscoil na Gaillimhe-University of GalwayGalwayIreland

Alzheimer's disease(AD)is the most common form of dementia worldwide,impairing memory and cognitive functions due to widespread neuronal *** global incidence of this neurodegenerative disorder is predicted to increase... 详细信息

关键词： Alzheimer death EAAT2

Clues from a missense mutation of the adenosine A1 receptor gene associated with early-onset Parkinson’s disease

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Neural Regeneration Research 2023年第10期18卷 2204-2205页

作者： Sergi Ferré Leonardo Pardo Francisco Ciruela Integrative Neurobiology Section National Institute on Drug AbuseIntramural Research ProgramNational Institutes of HealthBaltimoreMDUSA Laboratory of Computational Medicine Biostatistics UnitFaculty of MedicineUniversitat Autònoma BarcelonaBellaterraBarcelonaSpain Pharmacology Unit Department of Pathology and Experimental TherapeuticsSchool of Medicine and Health SciencesInstitute of NeurosciencesUniversity of Barcelona.Neuropharmacology&Pain GroupNeuroscience ProgramBellvitge Institute for Biomedical ResearchL’Hospitalet de LlobregatSpain

Parkinson’s disease (P D) is a com plex neu rodegenerative disorder for which ra re and common genetic variants contribute to disease risk,onset,and *** genetic contribution to PD can be classified mainly in,first,rare DNA variants that are highly penetrant and therefore causal,which are typically associated with monogenic PD;and second,more common risk polymorphic variants,which individually exert a small increase in the risk of the disease,which are usually identified in the most prevalent and apparently sporadic PD (Blauwendraat et al.,2020).

关键词： typically degenerative

Do tau-synaptic long-term depression interactions in the hippocampus play a pivotal role in the progression of Alzheimer’s disease?

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Neural Regeneration Research 2023年第6期18卷 1213-1219页

作者： Zhengtao Hu Tomas Ondrejcak Pengpeng Yu Yangyang Zhang Yin Yang Igor Klyubin Sean P.Kennelly Michael J.Rowan Neng-Wei Hu department of Physiology and Neurobiology School of Basic Medical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina department of Gerontology The First Affiliated Hospital of Wannan Medical CollegeWuhuAnhui ProvinceChina department of Pharmacology&therapeutics and Institute of neuroscience Trinity CollegeDublinIreland department of Age-Related Healthcare Tallaght University HospitalDublinIreland department of Medical Gerontology Trinity CollegeDublinIreland

Cognitive decline in Alzheimer’s disease correlates with the extent of tau pathology,in particular tau hyperphosphorylation that initially appears in the transentorhinal and related regions of the brain including the *** evidence indicates that tau hyperphosphorylation caused by either amyloid-βor long-term depression,a form of synaptic weakening involved in learning and memory,share similar *** from our group and others demonstrate that long-term depression-inducing low-frequency stimulation triggers tau phosphorylation at different residues in the hippocampus under different experimental conditions including ***,certain forms of long-term depression at hippocampal glutamatergic synapses require endogenous tau,in particular,phosphorylation at residue *** the exact mechanisms of interaction between tau and long-term depression may help our understanding of the physiological and pathological functions of tau/tau(hyper)*** first summarize experimental evidence regarding tau-long-term depression interactions,followed by a discussion of possible mechanisms by which this interplay may influence the pathogenesis of Alzheimer’s ***,we conclude with some thoughts and perspectives on future research about these interactions.

关键词： aging Alzheimer’s disease amyloid-β Aβoligomers hippocampus long-term depression long-term potentiation LTD LTP metabotropic glutamate receptor N-methyl-D-aspartate receptor tau hyperphosphorylation tau phosphorylation tau

Two-step production of monoamines in monoenzymatic cells in the spinal cord:a different control strategy of neurotransmitter supply?

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Neural Regeneration Research 2016年第12期11卷 1904-1909页

作者： Mengliang Zhang Neuronano Research Center Department of Experimental Medical ScienceLund University department of neuroscience and Pharmacology University of Copenhagen

Monoamine neurotransmitters play an important role in the modulation of sensory, motor and autonomic functions in the spinal cord. Although traditionally it is believed that in mammalian spinal cord, monoamine neurotransmitters mainly originate from the brain, accumulating evidence indicates that especially when the spinal cord is injured, they can also be produced in the spinal cord. In this review, I will present evidence for a possible pathway for two-step synthesis of dopamine and serotonin in the spinal cord. Published data from different sources and unpublished data from my own ongoing projects indicate that monoenzymatic cells expressing aromatic L-amino acid decarboxylase（AADC）, tyrosine hydroxylase（TH） or tryptophan hydroxylase（TPH） are present in the spinal cord and that these TH and THP cells often lie in close proximity to AADC cells. Prompted by the above evidence, I hypothesize that dopamine and serotonin could be synthesized sequentially in two monoenzymatic cells in the spinal cord via a TH-AADC and a TPH-AADC cascade respectively. The monoamines synthesized through this pathway may compensate for lost neurotransmitters following spinal cord injury and also may play specific roles in the recovery of sensory, motor and autonomic functions.

关键词： non-monoaminergic cell monoamine precursor 5-hydroxytryptophan L-dopa serotonin dopamine tyrosine hydroxylase tryptophan hydroxylase aromatic L-amino acid decarboxylase spinal cord injury