James Lee, Natalie Pye, Laura Ellis, Kurt De Vos, Heather Mortiboys
{"title":"Evidence of mitochondrial dysfunction in ALS and methods for measuring in model systems.","authors":"James Lee, Natalie Pye, Laura Ellis, Kurt De Vos, Heather Mortiboys","doi":"10.1016/bs.irn.2024.04.006","DOIUrl":"10.1016/bs.irn.2024.04.006","url":null,"abstract":"<p><p>Metabolic dysfunction is a hallmark of multiple amyotrophic lateral sclerosis (ALS) models with a majority of ALS patients exhibiting hypermetabolism. The central sites of metabolism in the cell are mitochondria, capable of utilising a multitude of cellular substrates in an array of ATP-generating reactions. With reactive oxygen species (ROS) production occurring during some of these reactions, mitochondria can contribute considerably to oxidative stress. Mitochondria are also very dynamic organelles, interacting with other organelles, undergoing fusion/fission in response to changing metabolic states and being turned over by the cell regularly. Disruptions to many of these mitochondrial functions and processes have been reported in ALS models, largely indicating compromised mitochondrial function, increased ROS production by mitochondria, disrupted interactions with the endoplasmic reticulum and reduced turnover. This chapter summarises methods routinely used to assess mitochondria in ALS models and the alterations that have been reported in these models.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"176 ","pages":"269-325"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159328","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":"Recent advances in the genetics of familial and sporadic ALS.","authors":"Ammar Al-Chalabi, Jinsy Andrews, Sali Farhan","doi":"10.1016/bs.irn.2024.04.007","DOIUrl":"10.1016/bs.irn.2024.04.007","url":null,"abstract":"<p><p>ALS shows complex genetic inheritance patterns. In about 5% to 10% of cases, there is a family history of ALS or a related condition such as frontotemporal dementia in a first or second degree relative, and for about 80% of such people a pathogenic gene variant can be identified. Such variants are also seen in people with no family history because of factor influencing the expression of genes, such as age. Genetic susceptibility factors also contribute to risk, and the heritability of ALS is between 40% and 60%. The genetic variants influencing ALS risk include single base changes, repeat expansions, copy number variants, and others. Here we review what is known of the genetic landscape and architecture of ALS.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"176 ","pages":"49-74"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159334","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":"Use of biomarkers in clinical trials and future developments that will help identify novel biomarkers.","authors":"Andrea Malaspina","doi":"10.1016/bs.irn.2024.04.010","DOIUrl":"10.1016/bs.irn.2024.04.010","url":null,"abstract":"<p><p>Engineering new solutions for therapeutic benefit in Amyotrophic Lateral Sclerosis (ALS) has proved a difficult task to accomplish. This is largely the reflection of complexities at multiple levels, that require solutions to improve cost-effectiveness and outcomes. The main obstacle related to the condition's clinical heterogeneity, chiefly the broad difference in survival observed among ALS patients, imposes large populations studies and long follow-up to evaluate any efficacy. The emerging solution is composite clinical and biological parameters enabling prognostic stratification into homogeneous phenotypes for more affordable studies. From a therapeutic development perspective, the choice of a medicinal product requires the availability of treatment-specific biomarkers of target engagement to identify off-target effects based on the compound's putative modality of action. More importantly, there are no established biomarkers of treatment response that can complement clinical outcome measures and support futility and end of treatment analyses of efficacy. Ultimately the onus rests on the development of biomarkers encompassing the unmet needs of clinical trial design, from inclusion to efficacy. These readouts of the pathological process may be used in combination with clinical and paraclinical outcome measured, significantly reducing the time and financial burden of clinical studies. Progress towards a biomarker-driven clinical trial design in ALS has been possible thanks to the accurate detection of neurofilaments and of other immunological mediators in biological fluids with the disease progression, a step change enabling the testing of novel therapeutic agents in a new clinical trial setting. However, further progress remains to be made to find treatment specific target engagement biomarkers along with readouts of treatment response that can be reliably applied to all emerging therapies and clinical studies. Here we will cover the basic notions of biomarker development in ALS clinical trials, the most crucial unanswered questions and the unmet needs in the ALS biomarkers space.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"176 ","pages":"171-207"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159339","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":"Review: Lower urinary tract dysfunction in animal models of Parkinson's disease (PD): Translational aspects for the treatment of PD patients with overactive bladder.","authors":"Takeya Kitta, Teruyuki Ogawa, Sadako Kuno, Hidehiro Kakizaki, Naoki Yoshimura","doi":"10.1016/bs.irn.2023.12.002","DOIUrl":"10.1016/bs.irn.2023.12.002","url":null,"abstract":"<p><p>Although the loss of dopaminergic neurons in the substantia nigra and consequent motor symptoms are the hallmarks of Parkinson's disease (PD), several non-motor symptoms may appear prior to these typical motor symptoms. While a variety of non-motor symptoms have emerged as the primary predictor of PD patients' quality of life, even though motor symptoms are undoubtedly distressing. According to a study, the prevalence of lower urinary tract symptoms (LUTS) varies between 27% and 64%, suggesting that PD-related lower urinary tract dysfunction may be affected by the disease stage, the presence of concomitant conditions affecting the lower urinary tract, and other autonomic dysfunctions. Animal models can serve as a platform for research into the causes of PD-related dysfunction and the evaluation of cutting-edge therapeutic approaches although the majority of animal research have been directed toward motor symptoms of PD. At present, the cause of lower urinary tract dysfunction in PD has not been fully clarified although the increasing evidence showing the multiple mechanisms underlying PD-related LUTS has emerged. In this chapter we summarize the findings of basic research in the studies of the lower urinary tract dysfunction using with different animal PD models and we try to shed light on the translational aspects for the development of future treatment modalities in PD patients with LUTS.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"174 ","pages":"211-230"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716768","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":"Preface.","authors":"Elaine Del-Bel, Felipe V Gomes, Sabrina F Lisboa","doi":"10.1016/S0074-7742(24)00099-0","DOIUrl":"https://doi.org/10.1016/S0074-7742(24)00099-0","url":null,"abstract":"","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"177 ","pages":"xv-xvi"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141728486","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}
Rayssa C Briânis, Fabrício A Moreira, Lia P Iglesias
{"title":"Cannabidiol and addiction.","authors":"Rayssa C Briânis, Fabrício A Moreira, Lia P Iglesias","doi":"10.1016/bs.irn.2024.03.006","DOIUrl":"10.1016/bs.irn.2024.03.006","url":null,"abstract":"<p><p>Cannabidiol (CBD) has been investigated for several therapeutic applications, having reached the clinics for the treatment of certain types of epilepsies. This chapter reviews the potential of CBD for the treatment of substance use disorders (SUD). We will present a brief introduction on SUD and current treatments. In the second part, preclinical and clinical studies with CBD are discussed, focusing on its potential therapeutic application for SUD. Next, we will consider the potential molecular mechanism of action of CBD in SUD. Finally, we will summarize the main findings and perspectives in this field. There is a lack of studies on CBD and SUD in comparison to the extensive literature investigating the use of this phytocannabinoid for other neurological and psychiatric disorders, such as epilepsy. However, the few studies available do suggest a promising role of CBD in the pharmacotherapy of SUD, particularly related to cocaine and other psychostimulant drugs.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"177 ","pages":"319-333"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141728476","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}
Lianyuan Feng, Aruna Sharma, Zhenguo Wang, Dafin F Muresanu, Z Ryan Tian, José Vicente Lafuente, Anca D Buzoianu, Ala Nozari, Cong Li, Ziquiang Zhang, Chen Lin, Hongyun Huang, Igor Manzhulo, Lars Wiklund, Hari Shanker Sharma
{"title":"Nanowired delivery of dl-3-n-butylphthalide with antibodies to alpha synuclein potentiated neuroprotection in Parkinson's disease with emotional stress.","authors":"Lianyuan Feng, Aruna Sharma, Zhenguo Wang, Dafin F Muresanu, Z Ryan Tian, José Vicente Lafuente, Anca D Buzoianu, Ala Nozari, Cong Li, Ziquiang Zhang, Chen Lin, Hongyun Huang, Igor Manzhulo, Lars Wiklund, Hari Shanker Sharma","doi":"10.1016/bs.irn.2023.06.005","DOIUrl":"10.1016/bs.irn.2023.06.005","url":null,"abstract":"<p><p>Stress is one of the most serious consequences of life leading to several chronic diseases and neurodegeneration. Recent studies show that emotional stress and other kinds of anxiety and depression adversely affects Parkinson's disease symptoms. However, the details of how stress affects Parkinson's disease is still not well known. Traumatic brain injury, stroke, diabetes, post-traumatic stress disorders are well known to modify the disease precipitation, progression and persistence. However, show stress could influence Parkinson's disease is still not well known. The present investigation we examine the role of immobilization stress influencing Parkinson's disease brain pathology in model experiments. In ore previous report we found that mild traumatic brain injury exacerbate Parkinson's disease brain pathology and nanodelivery of dl-3-n-butylphthalide either alone or together with mesenchymal stem cells significantly attenuated Parkinson's disease brain pathology. In this chapter we discuss the role of stress in exacerbating Parkinson's disease pathology and nanowired delivery of dl-3-n-butylphthalide together with monoclonal antibodies to alpha synuclein (ASNC) is able to induce significant neuroprotection. The possible mechanisms of dl-3-n-butylphthalide and ASNC induced neuroprotection and suitable clinical therapeutic strategy is discussed.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"171 ","pages":"47-82"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41143353","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":"Adenosine A<sub>2A</sub> receptors and sleep.","authors":"Mustafa Korkutata, Michael Lazarus","doi":"10.1016/bs.irn.2023.04.007","DOIUrl":"https://doi.org/10.1016/bs.irn.2023.04.007","url":null,"abstract":"<p><p>Adenosine, a known endogenous somnogen, induces sleep via A<sub>1</sub> and A<sub>2A</sub> receptors. In this chapter, we review the current knowledge regarding the role of the adenosine A<sub>2A</sub> receptor and its agonists, antagonists, and allosteric modulators in sleep-wake regulation. Although many adenosine A<sub>2A</sub> receptor agonists, antagonists, and allosteric modulators have been identified, only a few have been tested to see if they can promote sleep or wakefulness. In addition, the growing popularity of natural sleep aids has led to an investigation of natural compounds that may improve sleep by activating the adenosine A<sub>2A</sub> receptor. Finally, we discuss the potential therapeutic advantage of allosteric modulators of adenosine A<sub>2A</sub> receptors over classic agonists and antagonists for treating sleep and neurologic disorders.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"170 ","pages":"155-178"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41169557","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}
Hari Shanker Sharma, Lianyuan Feng, Dafin F Muresanu, Z Ryan Tian, José Vicente Lafuente, Anca D Buzoianu, Ala Nozari, Igor Bryukhovetskiy, Igor Manzhulo, Lars Wiklund, Aruna Sharma
{"title":"Stress induced exacerbation of Alzheimer's disease brain pathology is thwarted by co-administration of nanowired cerebrolysin and monoclonal amyloid beta peptide antibodies with serotonin 5-HT6 receptor antagonist SB-399885.","authors":"Hari Shanker Sharma, Lianyuan Feng, Dafin F Muresanu, Z Ryan Tian, José Vicente Lafuente, Anca D Buzoianu, Ala Nozari, Igor Bryukhovetskiy, Igor Manzhulo, Lars Wiklund, Aruna Sharma","doi":"10.1016/bs.irn.2023.05.018","DOIUrl":"10.1016/bs.irn.2023.05.018","url":null,"abstract":"<p><p>Alzheimer's disease is one of the devastating neurodegenerative diseases affecting mankind worldwide with advancing age mainly above 65 years and above causing great misery of life. About more than 7 millions are affected with Alzheimer's disease in America in 2023 resulting in huge burden on health care system and care givers and support for the family. However, no suitable therapeutic measures are available at the moment to enhance quality of life to these patients. Development of Alzheimer's disease may reflect the stress burden of whole life inculcating the disease processes of these neurodegenerative disorders of the central nervous system. Thus, new strategies using nanodelivery of suitable drug therapy including antibodies are needed in exploring neuroprotection in Alzheimer's disease brain pathology. In this chapter role of stress in exacerbating Alzheimer's disease brain pathology is explored and treatment strategies are examined using nanotechnology based on our own investigation. Our observations clearly show that restraint stress significantly exacerbate Alzheimer's disease brain pathology and nanodelivery of a multimodal drug cerebrolysin together with monoclonal antibodies (mAb) to amyloid beta peptide (AβP) together with a serotonin 5-HT6 receptor antagonist SB399885 significantly thwarted Alzheimer's disease brain pathology exacerbated by restraint stress, not reported earlier. The possible mechanisms and future clinical significance is discussed.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"171 ","pages":"3-46"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41176457","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}
Susana Bulnes, Marina Picó-Gallardo, Harkaitz Bengoetxea, José Vicente Lafuente
{"title":"Effects of curcumin nanodelivery on schizophrenia and glioblastoma.","authors":"Susana Bulnes, Marina Picó-Gallardo, Harkaitz Bengoetxea, José Vicente Lafuente","doi":"10.1016/bs.irn.2023.05.013","DOIUrl":"10.1016/bs.irn.2023.05.013","url":null,"abstract":"<p><p>Curcumin is a natural polyphenol, which has a variety of pharmacological activities, including, antineoplastic, antioxidative and neuroprotective effects. Recent studies provided evidence for the bioactive role of curcumin in the prevention and treatment of various central nervous system (CNS)-related diseases including Parkinson's, Alzheimer's, Schizophrenia disease and glioma neoplasia. Schizophrenia is a disabling psychiatric disorder related with an aberrant functional coupling between hippocampus and prefrontal cortex that might be crucial for cognitive dysfunction. Animal studies have lent support to the hypothesis that curcumin could improve cognitive functioning and enhance cell proliferation of dentate gyrus. In relation to brain tumors, specifically gliomas, the antineoplastic action of curcumin is based on the inhibition of cell growth promoting apoptosis or autophagy and preventing angiogenesis. However, one of the main impediments for the application of curcumin to patients is its low bioavailability. In intracranial lesions, curcumin has problems to cross the blood-brain barrier (BBB). Currently nano-based drug delivery systems are opening a new horizon to tackle this problem. The bioavailability and effective release of curcumin can be made possible in the form of nanocurcumin. This nanoformulation preserves the properties of curcumin and makes it reach tissues with pathology. This review try to study the beneficial effects of the curcumin nanodelivery in central nervous pathologies such us schizophrenia and glioma disease.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"171 ","pages":"163-203"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41157632","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}