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A systematic review of progenitor survival and maturation in Parkinsonian models

Neural Regeneration Research 2025年第11期20卷 3172-3178页

作者： Giulia Comini Eilís Dowd pharmacology&therapeutics and galway neuroscience center University of GalwayGalwayIreland

Stem cell-based brain repair is a promising emergent therapy for Parkinson's disease based on years of foundational research using human fetal donors as a cell *** current therapeutic options for patients,this approach has the potential to provide longterm stem cell–derived reconstruction and restoration of the dopaminergic input to denervated regions of the brain allowing for restoration of certain functions to *** ultimate clinical success of stem cell–derived brain repair will depend on both the safety and efficacy of the approach and the latter is dependent on the ability of the transplanted cells to survive and differentiate into functional dopaminergic neurons in the Parkinsonian *** the pre-clinical literature suggests that there is considerable variability in survival and differentiation between studies,the aim of this systematic review was to assess these parameters in human stem cell-derived dopaminergic progenitor transplant studies in animal models of Parkinson's disease.A defined systematic search of the PubMed database was completed to identify relevant studies published up to March *** screening,76 articles were included in the analysis from which 178 separate transplant studies were *** these,graft survival could be assessed in 52 studies and differentiation in 129 ***,we found that graft survival ranged from<1% to 500% of cells transplanted,with a median of 51%of transplanted cells surviving in the brain;while dopaminergic differentiation of the cells ranged from 0% to 46% of cells transplanted with a median of 3%.This systematic review suggests that there is considerable scope for improvement in the differentiation of stem cell-derived dopaminergic progenitors to maximize the therapeutic potential of this approach for patients.

关键词： cell replacement therapy differentiation embryonic stem cells graft induced pluripotent stem cells Parkinson's disease survival transplant

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Glial response in the midcingulate cortex in Huntington’s disease

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Neural Regeneration Research 2025年第1期20卷 207-208页

作者： Thulani H.Palpagama Andrea Kwakowsky center for Brain Research and Department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand pharmacology and therapeutics School of MedicineGalway Neuroscience CenterUniversity of GalwayGalwayIreland

Huntington’s disease(HD)is a genetic disease characterized by the progressive degeneration of the striatum and *** can present with a variety of symptoms that can broadly be classified into motor symptoms,inclusive of choreatic movements and rigidity,mood and psychiatric symptoms,such as depression and apathy,and cognitive symptoms,such as cognitive *** causal mutation underlying HD results from an expansion of a CAG repeat sequence on the IT15 gene,resulting in the formation and accumulation of a mutant huntingtin protein.

关键词： Huntington degeneration cortex

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Neuroinflammation as a therapeutic target in Huntington's disease

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Neural Regeneration Research 2025年第3期20卷 817-818页

作者： Andrea Kwakowsky Thulani H.Palpagama center for Brain Research and Department of Anatomy and Medical Imaging Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand pharmacology and therapeutics School of MedicineGalway Neuroscience CentreUniversity of GalwayGalwayIreland

In 1872, George Huntington presented his essay “On Chorea” to the Meigs and Mason Academy of Medicine and, in doing so, detailed a disease that would later bear his name. Huntington's disease(HD) is a genetic, neurodegenerative disease that manifests as the loss of motor control,cognitive impairment,and mood and psychiatric changes in paents.

关键词： Huntington inflammation Medicine

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Brain repair for Parkinson's disease:is the answer in the matrix?

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Neural Regeneration Research 2018年第7期13卷 1187-1188页

作者： Niamh Moriarty Eilís Dowd pharmacology & therapeutics and galway neuroscience Centre National University of Ireland

Two hundred years after James Parkinson first described the cardinal motor symptoms of the disorder that would later bear his name,there is still an irrefutable need for a therapy that targets the underlying pathophys... 详细信息

关键词： Brain repair for Parkinson’s disease:is the answer in the matrix

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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

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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

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Central CB2 receptors in inflammation-driven neurodegeneration： dysregulation and therapeutic potential

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Neural Regeneration Research 2016年第9期11卷 1409-1410页

作者： Ruth M. Concannon Eilis Dowd pharmacology & therapeutics and galway neuroscience Centre National University of Ireland Galway Ireland

In recent times there has been an intensification of interest in the pathological role of neuroinflammation in neurodegenerative disease. Neuroprotective strategies to slow, halt or reverse neuro- degeneration have not proven fruitful clinically, and the notion of a multi-hit hypothesis in the progression of neurodegenerative disease has steered focus towards other contributory pathological factors, particularly neuroinflammation. Neuroinflammation is believed to sustain the neurodegenerative pathology, forming a cy- clical and self-sustaining pathological process, with dying neurons activating microglia, which, once activated, can release several fac- tors that kill further neurons （reviewed in Blandini, 2013）.

关键词： Central CB2 receptors in inflammation-driven neurodegeneration CB

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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

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Basics on the use of acid-sensing ion channels' inhibitors as therapeutics

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Neural Regeneration Research 2019年第3期14卷 395-398页

作者： Jamileh Dibas Houssam Al-Saad Adnan Dibas Faculty of Pharmacy Applied UniversityAmman Jordan North Texas Eye Research Institute Department of Pharmacology and Neuroscience University of North Texas Health Science Center at Fort Worth

Since the discovery of acid-sensing ion channels in 1997, their importance in the health of neurons and other non-neuronal cells has gained significant importance. Acid-sensing ion channels play important roles in mediating pain sensation during diseases such as stroke, inflammation, arthritis, cancer, and recently migraine. More interestingly, acid-sensing ion channels may explain the sex differences in pain between males and females. Also, the ability of acid-sensing ion channel blockers to exert neuroprotective effects in a number of neurodegenerative diseases has added a new dimension to their therapeutic value. The current failure rate of ～45% of new drugs(due to toxicity issues) and saving of up to 7 years in the life span of drug approval makes drug repurposing a high priority. If acid-sensing ion channels' blockers undergo what is known as "drug repurposing", there is a great potential to bring them as medications with known safety profiles to new patient populations. However, the route of administration remains a big challenge due to their poor penetration of the blood brain and retinal barriers. In this review, the promise of using acid-sensing ion channel blockers as neuroprotective drugs is discussed.

关键词： optic nerve glaucoma neurodegeneration neuroprotection acid sensing ion channel calpain

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Human immunodeficiency virus and hepatotropic viruses comorbidities as the inducers of liver injury progression

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World Journal of Gastroenterology 2019年第4期25卷 398-410页

作者： Murali Ganesan Larisa Y Poluektova Kusum K Kharbanda Natalia A Osna Research Service Veterans Affairs Nebraska-Western Iowa Health Care System Department of Internal Medicine University of Nebraska Medical Center Department of pharmacology and Experimental neuroscience University of Nebraska Medical Center

Hepatotropic viruses induced hepatitis progresses much faster and causes more liver-related health problems in people co-infected with human immunodeficiency virus(HIV). Although treatment with antiretroviral therapy has extended the life expectancy of people with HIV, liver disease induced by hepatitis B virus(HBV) and hepatitis C virus(HCV) causes significant numbers of non-acquired immune deficiency syndrome(AIDS)-related deaths in coinfected patients. In recent years, new insights into the mechanisms of accelerated fibrosis and liver disease progression in HIV/HCV and HIV/HBV co-infections have been reported. In this paper, we review recent studies examining the natural history and pathogenesis of liver disease in HIV-HCV/HBV co-infection in the era of direct acting antivirals(DAA) and antiretroviral therapy(ART). We also review the novel therapeutics for management of HIV/HCV and HIV/HBV coinfected individuals.

关键词： Human immunodeficiency virus Hepatitis C virus Hepatitis B virus Fibrosis Stiffness Treatment

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