Neurodegeneration最新文献

{"title":"Unlocking the Potential: Repurposing Drugs for Neurodegeneration","authors":"Kangkan Deka, Tutumoni Kalita, Bhargab Thakuria, Renaldy Donlang Nongbet, Iman Bhaduri, Gitima Deka, Vivek P. Chavda","doi":"10.1201/9781998511839-9","DOIUrl":"https://doi.org/10.1201/9781998511839-9","url":null,"abstract":"Neurodegenerative disorders pose significant challenges to global healthcare systems due to their life-threatening impact on human beings and society. Currently, neurodegenerative disorders are not curable, and the medications available merely control the symptoms or slow the disease 204progression. This necessitates the exploration of new treatment strategies. The intricate structure of the nervous system and the challenges posed by the blood-brain barrier make the development of new drugs for neuropathological conditions more challenging compared to diseases affecting other organs. Drug repurposing has emerged as a promising strategy to address these problems in recent years. Repurposing involves identifying and investigating the therapeutic potential of existing drugs approved for other indications, thereby accelerating the drug development process and minimizing expenses. For instance, kinase inhibitors, which originally emerged as anti-cancer agents, have shown neuroprotective effects in neurological disorders. This chapter addresses neurodegenerative drug repurposing, using various approaches including computational and experimental investigations. Additionally, the chapter highlights information on approved repurposed drugs as well as drugs that are under investigation and have demonstrated promising results in clinical trials against neurodegenerative diseases. The chapter also emphasizes the significance of regulatory authorities, industries, and academics working together to effectively bring repurposed medicines to clinical practice.","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"1 1","pages":"203-255"},"PeriodicalIF":0.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147886454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Approved Treatment Strategies for Neurodegenerative Diseases","authors":"K. Sandhanam, Bedanta Bhattacharjee, T. Tamilanban, Ram Kumar Sahu, Ajayi Ayodeji Folorunsho, Rajashri Bezbaruah","doi":"10.1201/9781998511839-8","DOIUrl":"https://doi.org/10.1201/9781998511839-8","url":null,"abstract":"More than 6 million Americans are affected by neurodegenerative illnesses (NDI), and according to current projections, rates will quadruple in the 154next 30 years. The gradual loss of neurons, synapses, dendrites, and myelin in the central and/or peripheral nervous systems is a hallmark of NDI. Neurodegenerative diseases (NDDs) are chronic conditions brought on by environmental, physiological, genetic, and epigenetic causes. Dysregulation of the genome and the epigenome results in neurodegeneration. Neuroinflammation frequently results in the degeneration of neuronal cells. Aging increases mitochondrial DNA mutation rates faster than nuclear DNA. The frequency and severity of inflammatory demyelinating episodes, which constitute a defining feature of NDDs, are decreased by immunomodulatory treatments. We summarize the implications of gut microbiota, relapse management medications, psychotherapy, speech therapy, physical therapy, physical rehabilitation, and mental health counseling in NDDs that will be beneficial for understanding the etiology and progression of NDDs, which may in turn help in developing NDD interventions and clinical treatments for these diseases. This chapter focuses on the updated information on the etiology, hallmarks, molecular mechanisms, development, diagnosis, and approved therapeutic strategies of NDDs to reduce both the propagation of the ailment and slow down its progression.","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"1 1","pages":"153-201"},"PeriodicalIF":0.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147901602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurochemical Correlates of Dementia","authors":"Andrew W. Procter","doi":"10.1006/neur.1996.0054","DOIUrl":"10.1006/neur.1996.0054","url":null,"abstract":"<div><p>Studies of the neurochemical pathology of AD have indicated that early in the course of the disease, abnormalities of relatively few neurotransmitters are obvious. The most reliable and consistent changes are those seen in the cholinergic innervation of the cortex and the cortical pyramidal neurones. However, by the time of death there is usually considerable involvement of other neurones.</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 4","pages":"Pages 403-407"},"PeriodicalIF":0.0,"publicationDate":"1996-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20065846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cortical Connections and the Pathology of Alzheimer's Disease","authors":"R.C.A. Pearson","doi":"10.1006/neur.1996.0058","DOIUrl":"10.1006/neur.1996.0058","url":null,"abstract":"<div><p>The hypothesis that the distribution of neurodegeneration in Alzheimer's disease results from the spread of the pathology via anatomical connections is reviewed in the light of recent advances in knowledge of the connectivity of the cerebral cortex. Current understanding of cortical connections allows a more detailed examination of the distribution of pathology, particularly neurofibrillary tangles, in relation to this hypothesis. In particular, quantitative assessment of corticocortical pathways opens up the possibility of specific testing of the hypothesis. Theoretical considerations are discussed, and a predicted spread of pathology beginning in the olfactory centres of the medial temporal lobe and spreading retrogradely via known pathways is presented.</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 4","pages":"Pages 429-434"},"PeriodicalIF":0.0,"publicationDate":"1996-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20065850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maltol (3-hydroxy-2-methyl-4-pyrone) Toxicity in Neuroblastoma Cell Lines and Primary Murine Fetal Hippocampal Neuronal Cultures","authors":"Masaya Hironishi ,&nbsp;Masaya Hironishi ,&nbsp;Radzislaw Kordek ,&nbsp;Richard Yanagihara ,&nbsp;Ralph M. Garruto","doi":"10.1006/neur.1996.0044","DOIUrl":"10.1006/neur.1996.0044","url":null,"abstract":"<div><p>Maltol (3-hydroxy-2-methyl-4-pyrone), a product of carbohydrate degradation, is known to enhance aluminium-induced neurofibrillary degeneration in neuronal systems, but few toxicological studies have been conducted. We report maltol toxicity in neuroblastoma cell lines of mouse (Neuro 2a) and human (IMR 32) origin, and in primary murine fetal hippocam-pal neuronal cultures. As determined by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy-methoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] conversion, maltol exhibited a dose-dependent toxicity on the viability of both neuroblastoma cell lines, but the toxicity was more pronounced in Neuro 2a cells. Maltol was also toxic in a dose-dependent manner in primary murine fetal hippocampal neurons at micromolar concentrations. Electrophoresis of DNA extracted from maltol-intoxicated cells showed a laddering pattern, suggestive of apop-totic cell death. In the maltol-exposed hippocampal neuronal cultures, fragmented DNA ends were visualized<em>in situ</em>in morphologically condensed nuclei by terminal deoxynucleotidyl transferase with digoxigenin-labelled UTP and subsequent immunohistochemistry. Collectively, our findings suggest that the toxic effect of maltol is mediated through apoptosis. Further toxicological investigations are warranted, since maltol is found in the daily diet of humans.</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 4","pages":"Pages 325-329"},"PeriodicalIF":0.0,"publicationDate":"1996-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20065898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Neurotoxin MPTP Causes Degeneration of Specific Nucleus A8, A9 and A10 Dopaminergic Neurons in the Mouse","authors":"Dwight C. German ,&nbsp;Eric L. Nelson ,&nbsp;Chang-Lin Liang ,&nbsp;Samuel G. Speciale ,&nbsp;Christopher M. Sinton ,&nbsp;Patricia K. Sonsalla","doi":"10.1006/neur.1996.0041","DOIUrl":"10.1006/neur.1996.0041","url":null,"abstract":"<div><p>The neurotoxin MPTP has been used to create an animal model of Parkinson's disease in the mouse, in part, because it causes a significant loss of dopaminergic neurons in the substantia nigra (nucleus A9). The purpose of the present study was to determine whether MPTP also causes degeneration of midbrain dopaminergic neurons in nuclei A8 and A10 in the mouse, as occurs in humans with Parkinson's disease. Two commonly used strains of mice were used: FVB/N and C57BL/6. MPTP was administered in cumulative doses of 50—300 mg/kg. Seven days later, dopamine concentrations were measured in the striatum using high performance liquid chromatography, and midbrain dopaminergic neurons were identified using an antibody against tyrosine hydroxylase. The cell locations were mapped with a computer imaging system. In the FVB/N strain, there was a dose-dependent decrease in striatal dopamine concentrations. Although the highest dose (300 mg/kg) caused an 86% reduction in striatal dopamine concentrations, there was only a moderate and non-significant loss of midbrain dopaminergic neurons. In the C57BL/6 strain, however, a high dose of MPTP (240 mg/kg) caused a significant reduction in both striatal dopamine concentrations (95%), and midbrain dopaminergic cells; 69% loss of nucleus A8 cells, 75% loss of nucleus A9 cells, and in nucleus A10 subnuclei there was 42% loss of ventral tegmental area cells, 55% loss of interfascicular nucleus cells, and no loss of cells in the central linear nucleus. These data (1) provide further evidence for differential susceptibility to MPTP toxicity among different mouse strains, (2) indicate that a significant depletion of striatal dopamine is not necessarily due to degeneration of midbrain dopaminergic neurons, (3) provide the precise locations of midbrain dopaminergic cells that are vulnerable to MPTP, which will aid future studies that seek to determine the mechanism/s by which MPTP selectively destroys only certain midbrain dopaminergic neurons, and (4) indicate that MPTP produces midbrain dopaminergic neuronal degeneration in the same nuclei in the C57BL16 mouse that degenerate in humans with Parkinson's disease..</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 4","pages":"Pages 299-312"},"PeriodicalIF":0.0,"publicationDate":"1996-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20066756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective Effect of Recombinant Neutrophil Inhibitory Factor in Transient Focal Cerebral Ischaemia in the Rat","authors":"Kenneth B. Mackay,&nbsp;Sarah J. Bailey,&nbsp;Penelope D. King,&nbsp;Sara Patel,&nbsp;Thomas C. Hamilton,&nbsp;Colin A. Campbell","doi":"10.1006/neur.1996.0043","DOIUrl":"10.1006/neur.1996.0043","url":null,"abstract":"<div><p>The neuroprotective effects of recombinant neutrophil inhibitory factor (NIF) have been assessed with temporary (2 h) middle cerebral artery (MCA) occlusion in the rat using the intraluminal suture technique. Administration of NIF (1.5 mg/kg, i.v.) immediately after the onset of reperfusion and at 4 and 6 h post-MCA occlusion significantly reduced both hemispheric infarct volume (<em>P</em>&lt; 0.001) and brain swelling (<em>P</em>&lt; 0.001), and improved neurological outcome (<em>P</em>&lt; 0.02) when assessed at 24 h. These results demonstrate the marked neuroprotective efficacy of NIF in a rat model of transient focal cerebral ischaemia</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 4","pages":"Pages 319-323"},"PeriodicalIF":0.0,"publicationDate":"1996-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20066758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Bridging Concept: Optimizing Dose for Phase II/III in Alzheimer's Disease","authors":"Neal R. Cutler ,&nbsp;John J. Sramek ,&nbsp;John R. Kilborn","doi":"10.1006/neur.1996.0071","DOIUrl":"10.1006/neur.1996.0071","url":null,"abstract":"<div><p>Our research has shown that the tolerance of Alzheimer's disease (AD) patients for anti-dementia compounds is frequently higher but occasionally lower than the tolerance of healthy young or elderly populations. Such differences can either pose safety problems in later efficacy studies if patients cannot tolerate the dosages previously deemed ‘safe’ in healthy populations, or interfere with determining efficacy if inadequate doses are employed. We recommend use of a ‘bridging study’, which optimizes dosage early in development by determining the maximum tolerated dose of a compound in patients. Consecutive panels of patients each receive higher doses of study drug until a minimum intolerated dose is reached. The dose immediately below this one is then considered the maximum tolerated dose. Careful subject selection, adequate facilities, and highly qualified, experienced personnel, are critical to the successful implementation of a bridging study. Correctly done, bridging can streamline the overall drug development process while making Phase II and III trials safer for patients, and has immense potential for accelerating the search for compounds that have efficacy in AD.</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 4","pages":"Pages 511-514"},"PeriodicalIF":0.0,"publicationDate":"1996-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20066529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain Energy Metabolism, Cognitive Function and Down-regulated Oxidative Phosphorylation in Alzheimer Disease","authors":"Stanley I. Rapoport,&nbsp;Kimmo Hatanpää,&nbsp;Daniel R. Brady,&nbsp;Krish Chandrasekaran","doi":"10.1006/neur.1996.0065","DOIUrl":"10.1006/neur.1996.0065","url":null,"abstract":"<div><p>Reduced brain glucose utilization in early stages of Alzheimer disease, as measured with<em>in vivo</em>positron emission tomography, reflects potentially reversible down-regulation of gene expression for oxidative phosphorylation within neuronal mitochondria. Such down-regulation may occur when neuronal energy demand is first reduced by synaptic dysfunction or loss.</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 4","pages":"Pages 473-476"},"PeriodicalIF":0.0,"publicationDate":"1996-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20066523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Index to Volume 5","authors":"","doi":"10.1006/neur.1996.0072","DOIUrl":"https://doi.org/10.1006/neur.1996.0072","url":null,"abstract":"","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 4","pages":"Pages i-vi"},"PeriodicalIF":0.0,"publicationDate":"1996-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137003368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}