Current Neuropharmacology最新文献

{"title":"Symptomatic Treatment of Extrapyramidal Hyperkinetic Movement Disorders.","authors":"Gregory de Boer, Robertus Maria Alfonsius de Bie, Bart Erik Kris Sylvain Swinnen","doi":"10.2174/1570159X22666240517161444","DOIUrl":"https://doi.org/10.2174/1570159X22666240517161444","url":null,"abstract":"<p><p>Extrapyramidal hyperkinetic movement disorders comprise a broad range of phenotypic phenomena, including chorea, dystonia, and tics. Treatment is generally challenging and individualized, given the overlapping phenomenology, limited evidence regarding efficacy, and concerns regarding the tolerability and safety of most treatments. Over the past decade, the treatment has become even more intricate due to advancements in the field of deep brain stimulation as well as optimized dopamine- depleting agents. Here, we review the current evidence for treatment modalities of extrapyramidal hyperkinetic movement disorders and provide a comprehensive and practical overview to aid the choice of therapy. Mechanism of action and practical intricacies of each treatment modality are discussed, focusing on dosing and adverse effect management. Finally, future therapeutic developments are also discussed.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lysosomal Channels as New Molecular Targets in the Pharmacological Therapy of Neurodegenerative Diseases via Autophagy Regulation.","authors":"Valentina Tedeschi, Silvia Sapienza, Raffaella Ciancio, Lorella Maria Teresa Canzoniero, Anna Pannaccione, Agnese Secondo","doi":"10.2174/1570159X22666240517101846","DOIUrl":"https://doi.org/10.2174/1570159X22666240517101846","url":null,"abstract":"<p><p>Besides controlling several organellar functions, lysosomal channels also guide the catabolic \"self-eating\" process named autophagy, which is mainly involved in protein and organelle quality control. Neuronal cells are particularly sensitive to the rate of autophagic flux either under physiological conditions or during the degenerative process. Accordingly, neurodegeneration occurring in Parkinson's (PD), Alzheimer's (AD), and Huntington's Diseases (HD), and Amyotrophic Lateral Sclerosis (ALS) as well as Lysosomal Storage Diseases (LSD) is partially due to defective autophagy and accumulation of toxic aggregates. In this regard, dysfunction of lysosomal ionic homeostasis has been identified as a putative cause of aberrant autophagy. From a therapeutic perspective, Transient Receptor Potential Channel Mucolipin 1 (TRPML1) and Two-Pore Channel isoform 2 (TPC2), regulating lysosomal homeostasis, are now considered promising druggable targets in neurodegenerative diseases. Compelling evidence suggests that pharmacological modulation of TRPML1 and TPC2 may rescue the pathological phenotype associated with autophagy dysfunction in AD, PD, HD, ALS, and LSD. Although pharmacological repurposing has identified several already used drugs with the ability to modulate TPC2, and several tools are already available for the modulation of TRPML1, many efforts are necessary to design and test new entities with much higher specificity in order to reduce dysfunctional autophagy during neurodegeneration.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is Antipsychotic Drug Use During Pregnancy Associated with Increased\u0000Malformation Rates and Worsening of Maternal and Infant Outcomes? A\u0000Systematic Review","authors":"Gabriele Sani, T. Callovini, O. M. Ferrara, Daniele Segatori, Stella Margoni, A. Simonetti, Francesco Maria Lisci, G. Marano, Alessia Fischetti, G. Kotzalidis, Federica Di Segni, Federica Fiaschè, D. Janiri, L. Moccia, G. Manfredi, Alessandro Alcibiade, Caterina Brisi, F. Grisoni, Gianmarco Stella, E. Bernardi, Andrea Brugnami, M. Ciliberto, M. C. Spera, R. Caso, Sara Rossi, Gianluca Boggio, Giulia Mastroeni, Francesca Abate, E. Conte, Anna Quintano, L. D. Chiara, Laura Monti, Giovanni Camardese, Lucio Rinaldi, A. Koukopoulos, D. Chieffo, G. Angeletti, Marianna Mazza","doi":"10.2174/1570159x22666240516151449","DOIUrl":"https://doi.org/10.2174/1570159x22666240516151449","url":null,"abstract":"\u0000\u0000There is much debate about continuing antipsychotic medication in patients who need it when\u0000they become pregnant because benefits must be weighed against potential teratogenic and malformation\u0000effects related to antipsychotics themselves. To address this, we conducted a systematic review on the\u0000PubMed, PsycINFO and CINHAL databases and the ClinicalTrials.gov register using the following strategy:\u0000(toxicity OR teratogenicity OR malformation* OR \"birth defect*\" OR \"congenital abnormality\" OR\u0000\"congenital abnormalities\" OR \"brain changes\" OR \"behavioral abnormalities\" OR \"behavioral abnormalities\")\u0000AND antipsychotic* AND (pregnancy OR pregnant OR lactation OR delivery OR prenatal OR\u0000perinatal OR post-natal OR puerperium) on September 27, 2023. We found 38 studies to be eligible. The\u0000oldest was published in 1976, while most articles were recent. Most studies concluded that the antipsychotics,\u0000especially the second-generation antipsychotics, were devoid of teratogenic potential, while few\u0000studies were inconclusive and recommended replication. Most authoritative articles were from the Boston\u0000area, where large databases were implemented to study the malformation potential of psychiatric drugs.\u0000Other reliable databases are from Northern European registers. Overall conclusions are that antipsychotics\u0000are no more related to malformations than the disorders themselves; most studies recommend that\u0000there are no reasons to discontinue antipsychotic medications in pregnancy.\u0000","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140965759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Silico Prediction of Quercetin Analogs for Targeting Death-Associated Protein Kinase 1 (DAPK1) Against Alzheimer's Disease.","authors":"Yilu Sun, Jia Zhao, Yizhu Lu, Fung Yin Ngo, Bo Shuai, Zhang-Jin Zhang, Yibin Feng, Jianhui Rong","doi":"10.2174/1570159X22666240515090434","DOIUrl":"https://doi.org/10.2174/1570159X22666240515090434","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) is a progressive neurodegenerative disorder that greatly affects the health and life quality of the elderly population. Existing drugs mainly alleviate symptoms but fail to halt disease progression, underscoring the urgent need for the development of novel drugs. Based on the neuroprotective effects of flavonoid quercetin in AD, this study was designed to identify potential AD-related targets for quercetin and perform in silico prediction of promising analogs for the treatment of AD. Database mining suggested death-associated protein kinase 1 (DAPK1) as the most promising AD-related target for quercetin among seven protein candidates. To achieve better biological effects for the treatment of AD, we devised a series of quercetin analogs as ligands for DAPK1, and molecular docking analyses, absorption, distribution, metabolism, and excretion (ADME) predictions, as well as molecular dynamics (MD) simulations, were performed. The energy for drug-protein interaction was predicted and ranked. As a result, quercetin-A1a and quercetin-A1a1 out of 19 quercetin analogs exhibited the lowest interaction energy for binding to DAPK1 than quercetin, and they had similar dynamics performance with quercetin. In addition, quercetin-A1a and quercetin-A1a1 were predicted to have better water solubility. Thus, quercetin-A1a and quercetin-A1a1 could be promising agents for the treatment of AD. Our findings paved the way for further experimental studies and the development of novel drugs.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Appraisal of the Neuroprotective Potentials of Isoeugenol Using In-vitro, In-vivo and In-silico Approaches","authors":"Bandar A. Alyami, Zeeshan Ahmad, Mehreen Ghufran, Mater H. Mahnashi, Abdul Sadiq, Muhammad Ayaz","doi":"10.2174/1570159x22666240329125626","DOIUrl":"https://doi.org/10.2174/1570159x22666240329125626","url":null,"abstract":"Background: Alzheimer's disease (AD) is a neurodegenerative condition that affects the elder population and is linked to behavioral instability and cognitive decline. Only a few drugs are approved for clinical management of AD. Volatile oils and their components exhibit diverse pharmacological potentials, including neuroprotective properties. The current study aimed to evaluate isoeugenol's neuroprotective potentials against cognitive impairments caused by scopolamine. Methods: Standard protocols were followed in the in-vitro antioxidant, cholinesterase inhibitory and molecular docking assays. Isoeugenol was initially evaluated for antioxidant potential using DPPH and ABTS free radicals scavenging assays. Subsequently, AChE/BChE inhibition studies were performed following Ellman’s assay. To assess the compound's binding effectiveness at the enzymes' target site, it was docked against the binding sites of cholinesterase. The effect of isoeugenol supplementation on scopolamine-induced amnesia was assessed using Shallow Water Maze (SWM), Y-Maze and Elevated Plus Maze (EPM) tests. Results: In DPPH and ABTS assays, isoeugenol exhibited considerable efficacy against free radicals with IC50 of 38.97 and 43.76 μg/mL, respectively. Isoeugenol revealed 78.39 ± 0.40% and 67.73 ± 0.03% inhibitions against AChE and BChE, respectively, at 1 mg/ml concentration. In docking studies, isoeugenol exhibited a docking score of -12.2390, forming two hydrogen bonds at the active site residues of AChE. Further, with a docking score of -10.1632, isoeugenol binds adequately to theBChE enzyme via two arene-hydrogen interactions and one hydrogen bond. Conclusion: Isoeugenol offered considerable protection against scopolamine-induced memory deficits and improved the special memory of the rodents.","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140889342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug Target to Alleviate Mitochondrial Dysfunctions in Alzheimer’s Disease: Recent Advances and Therapeutic Implications","authors":"Md. Ataur Rahman, MD. Hasanur Rahman, Hyewhon Rhim, Bonglee Kim","doi":"10.2174/1570159x22666240426091311","DOIUrl":"https://doi.org/10.2174/1570159x22666240426091311","url":null,"abstract":": Alzheimer's disease (AD) is a severe progressive neurodegenerative condition associated with neuronal damage and reduced cognitive function that primarily affects the aged worldwide. While there is increasing evidence suggesting that mitochondrial dysfunction is one of the most significant factors contributing to AD, its accurate pathobiology remains unclear. Mitochondrial bioenergetics and homeostasis are impaired and defected during AD pathogenesis. However, the potential of mutations in nuclear or mitochondrial DNA encoding mitochondrial constituents to cause mitochondrial dysfunction has been considered since it is one of the intracellular processes commonly compromised in early AD stages. Additionally, electron transport chain dysfunction and mitochondrial pathological protein interactions are related to mitochondrial dysfunction in AD. Many mitochondrial parameters decline during aging, causing an imbalance in reactive oxygen species (ROS) production, leading to oxidative stress in age-related AD. Moreover, neuroinflammation is another potential causative factor in AD-associated mitochondrial dysfunction. While several treatments targeting mitochondrial dysfunction have undergone preclinical studies, few have been successful in clinical trials. Therefore, this review discusses the molecular mechanisms and different therapeutic approaches for correcting mitochondrial dysfunction in AD, which have the potential to advance the future development of novel drug-based AD interventions.","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140889337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced Serum Brain-Derived Neurotrophic Factor in Infants Affected by Severe Bronchiolitis","authors":"Raffaella Nenna, Carla Petrella, Enea Bonci, Paola Papoff, Margherita di Jorgi, Laura Petrarca, Maria Giulia Conti, Christian Barbat, Alessandra Pietrangeli, Marco Fiore, Fabio Midulla, Brome Group","doi":"10.2174/1570159x22999240223153901","DOIUrl":"https://doi.org/10.2174/1570159x22999240223153901","url":null,"abstract":"Background: Bronchiolitis is an acute viral infection of the lower respiratory tract, typical of infants in their first year of life and causing hypoxia in the most serious cases. Bronchiolitis recognizes various demographic risk factors that are associated with greater clinical severity; however, no laboratory factors are yet able to correlate with the clinical severity. Neurotrophins as Brain-Derived Neurotrophic Factor (BDNF) are mediators of neuronal plasticity. BDNF is constitutively expressed in smooth muscle cells and epithelium of the lower respiratory tract, and as it is released during inflammatory conditions, serum levels may have a relevant role in the prognosis of infants with bronchiolitis. Objective: In the present pilot study, we aimed to disclose the presence of serum BDNF in infants hospitalized with bronchiolitis at discharge as a disease severity indicator. Methods and Results: Serum BDNF, measured at hospital discharge, was significantly lower in severe bronchiolitis (expressed as O2-supplemented infants). Furthermore, no changes were disclosed for the Tropomyosin receptor kinase B, the main BDNF receptor and neurofilament light chain, a biomarker of neuronal degeneration. Conclusion: Low serum BDNF in infants with severe bronchiolitis could be associated with a higher utilization by lung cells or with an altered production by lung cells. Therefore, further research is required to study if a decreased production or increased consumption of this biomarker is at the base of the above-mentioned findings.","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140586834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Insights into the Neurotoxicity of Melamine: A Comprehensive Review","authors":"Reza Naeimi, Fatemeh Safarpour, Hamid Askari, Maryam Ghasemi-Kasman","doi":"10.2174/1570159x22666240320133241","DOIUrl":"https://doi.org/10.2174/1570159x22666240320133241","url":null,"abstract":": Melamine, a heterocyclic nitrogen-rich triazine chemical compound, is widely used in various household products, including furniture, dinnerware, and kitchen appliances. The unauthorized addition of the mixture to various foodstuffs to misrepresent protein content resulted in catastrophic, frequently life-threatening health consequences for kids as well as canines and has garnered international attention. Numerous primary studies and evaluations have been focused on melamine toxicity's implications on kidney function. Despite the profusion of literature on melamine's nephrotoxicity, evidence regarding its toxicity to other organs remains scarce. A number of recent studies suggest melamine can disrupt central nervous system (CNS) function and bring about cognitive impairments, contradicting the commonly held belief that melamine's detrimental effects are limited to the urinary system. The accumulation of melamine in the body is linked to various adverse effects, including depression, impaired synaptic transmission, oxidative stress, and neurodegenerative diseases. Several mechanisms may lead to such complications. However, numerous safeguards against melamine accumulation have been identified. This review could shed light on the potential neurological effects and mechanisms underlying melamine toxicity. Afterward, we will dive into the body's possible protectivemechanisms against melamine-induced toxicity.","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140586754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut Microbiome in Alzheimer’s Disease: from Mice to Humans","authors":"Chang Liang, Resel Pereira, Yan Zhang, Olga L. Rojas","doi":"10.2174/1570159x22666240308090741","DOIUrl":"https://doi.org/10.2174/1570159x22666240308090741","url":null,"abstract":": Alzheimer's disease (AD) is the most prevalent type of dementia, but its etiopathogenesis is not yet fully understood. Recent preclinical studies and clinical evidence indicate that changes in the gut microbiome could potentially play a role in the accumulation of amyloid beta. However, the relationship between gut dysbiosis and AD is still elusive. In this review, the potential impact of the gut microbiome on AD development and progression is discussed. Pre-clinical and clinical literature exploring changes in gut microbiome composition is assessed, which can contribute to AD pathology including increased amyloid beta deposition and cognitive impairment. We also highlight the gut-brain axis and the potential involvement of metabolites produced by the gut microbiome in AD are also highlighted. Furthermore, the potential of antibiotics, prebiotics, probiotics, fecal microbiota transplantation, and dietary interventions as complementary therapies for the management of AD is summarized. This review provides valuable insights into potential therapeutic strategies to modulate the gut microbiome in AD.","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140150552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two Distinct Neuronal Populations in the Rat Parafascicular Nucleus Oppositely Encode the Engagement in Stimulus-driven Reward-seeking","authors":"Mehdi Sicre, Frederic Ambroggi, Julie Meffre","doi":"10.2174/1570159x22666240131114225","DOIUrl":"https://doi.org/10.2174/1570159x22666240131114225","url":null,"abstract":"Background:: The thalamus is a phylogenetically well-preserved structure. Known to densely contact cortical regions, its role in the transmission of sensory information to the striatal complex has been widely reconsidered in recent years. Methods:: The parafascicular nucleus of the thalamus (Pf) has been implicated in the orientation of attention toward salient sensory stimuli. In a stimulus-driven reward-seeking task, we sought to characterize the electrophysiological activity of Pf neurons in rats. Results:: We observed a predominance of excitatory over inhibitory responses for all events in the task. Neurons responded more strongly to the stimulus compared to lever-pressing and reward collecting, confirming the strong involvement of the Pf in sensory information processing. The use of long sessions allowed us to compare neuronal responses to stimuli between trials when animals were engaged in action and those when they were not. We distinguished two populations of neurons with opposite responses: MOTIV+ neurons responded more intensely to stimuli followed by a behavioral response than those that were not. Conversely, MOTIV- neurons responded more strongly when the animal did not respond to the stimulus. In addition, the latency of excitation of MOTIV- neurons was shorter than that of MOTIV+ neurons. Conclusion:: Through this encoding, the Pf could perform an early selection of environmental stimuli transmitted to the striatum according to motivational level","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140010991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}