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Alfalahi H, Dias SB, Khandoker AH, Chaudhuri KR, Hadjileontiadis LJ. A scoping review of neurodegenerative manifestations in explainable digital phenotyping. NPJ Parkinsons Dis 2023; 9:49. [PMID: 36997573 PMCID: PMC10063633 DOI: 10.1038/s41531-023-00494-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Accepted: 03/16/2023] [Indexed: 04/03/2023] Open
Abstract
Neurologists nowadays no longer view neurodegenerative diseases, like Parkinson's and Alzheimer's disease, as single entities, but rather as a spectrum of multifaceted symptoms with heterogeneous progression courses and treatment responses. The definition of the naturalistic behavioral repertoire of early neurodegenerative manifestations is still elusive, impeding early diagnosis and intervention. Central to this view is the role of artificial intelligence (AI) in reinforcing the depth of phenotypic information, thereby supporting the paradigm shift to precision medicine and personalized healthcare. This suggestion advocates the definition of disease subtypes in a new biomarker-supported nosology framework, yet without empirical consensus on standardization, reliability and interpretability. Although the well-defined neurodegenerative processes, linked to a triad of motor and non-motor preclinical symptoms, are detected by clinical intuition, we undertake an unbiased data-driven approach to identify different patterns of neuropathology distribution based on the naturalistic behavior data inherent to populations in-the-wild. We appraise the role of remote technologies in the definition of digital phenotyping specific to brain-, body- and social-level neurodegenerative subtle symptoms, emphasizing inter- and intra-patient variability powered by deep learning. As such, the present review endeavors to exploit digital technologies and AI to create disease-specific phenotypic explanations, facilitating the understanding of neurodegenerative diseases as "bio-psycho-social" conditions. Not only does this translational effort within explainable digital phenotyping foster the understanding of disease-induced traits, but it also enhances diagnostic and, eventually, treatment personalization.
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Affiliation(s)
- Hessa Alfalahi
- Department of Biomedical Engineering, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates.
- Healthcare Engineering Innovation Center (HEIC), Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates.
| | - Sofia B Dias
- Department of Biomedical Engineering, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
- Healthcare Engineering Innovation Center (HEIC), Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
- CIPER, Faculdade de Motricidade Humana, University of Lisbon, Lisbon, Portugal
| | - Ahsan H Khandoker
- Department of Biomedical Engineering, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
- Healthcare Engineering Innovation Center (HEIC), Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
| | - Kallol Ray Chaudhuri
- Parkinson Foundation, International Center of Excellence, King's College London, Denmark Hills, London, UK
- Department of Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, UK
| | - Leontios J Hadjileontiadis
- Department of Biomedical Engineering, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
- Healthcare Engineering Innovation Center (HEIC), Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
- Department of Electrical and Computer Engineering, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Faruk EM, Fouad H, Hasan RAA, Taha NM, El-Shazly AM. Inhibition of gene expression and production of iNOS and TNF-α in experimental model of neurodegenerative disorders stimulated microglia by Soy nano-isoflavone/stem cell-exosomes. Tissue Cell 2022; 76:101758. [PMID: 35182987 DOI: 10.1016/j.tice.2022.101758] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 02/02/2022] [Accepted: 02/09/2022] [Indexed: 12/16/2022]
Abstract
The present study evaluated the therapeutic potential of soybean nano-isoflavone extract versus bone marrow mesenchymal stem cells derived extracellular exosomes (BMSCs-EXs) in experimentally induced neurodegenerative diseases in rats (ND). In this study, 36 albino male rats were divided into four groups: Group I (control rats); Group II (induced neurodegenerative disease in rats by intraperitoneal injection of d-galactose (120 mg/kg/day for 2 months); Group III (ND-induced rats treated with nano-isoflavone in doses of 10 mg/kg by oral gavage for 3 months); and Group IV (ND-induced rats treated with a single dose injection of BMSCs-EXs. The effect of BMSCs-EXs was evaluated by cerebral oxidant/antioxidant biomarkers, and mRNA gene expression quantitation for cerebral tumor necrosis factor α (TNF-α), inducible nitric oxide synthase (i-NOS) and GAPDH pathway-encoding genes by real time reverse transcription polymerase chain reaction (RT-PCR) techniques. Then, histopathological examination of the cerebral cortical tissues. Our results showed that BMSC-EXs were successfully isolated and characterized. d-galactose produced a significant rise in the number of damaged neurons, decreased cerebral superoxide dismutase and catalase activities, increased cerebral malondialdehyde levels, downregulated the cerebral TNF-α, and i-NOS pathway-encoding genes. Furthermore, BMSC-EXs and nano-isoflavone treatments repaired damaged cerebral tissue and recovered its function greatly following induction of neurodegenerative disease. Treatment with either MSCs-EXs or nano-isoflavones led to significant improvement in the histological findings, reversed the degenerative effect of d-galactose, and had a favorable therapeutic utility against d- galactose-induced neurodegenerative disease.
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Affiliation(s)
- Eman Mohamed Faruk
- Department of Anatomy, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; Department of Histology & Cell Biology, Faculty of Medicine, Benha University, Egypt.
| | - Hanan Fouad
- Medical Biochemistry & Molecular Biology, Faculty of Medicine, Cairo University, Egypt; Galala University, Faculty of medicine, Suez Governorate, Egypt
| | - Rehab Abd Allah Hasan
- Department of Histology & Cell Biology, Faculty of Medicine for Girls; AFMG, Al-Azhar University Egypt
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Cunha LP, Pires LA, Cruzeiro MM, Almeida ALM, Martins LC, Martins PN, Shigaeff N, Vale TC. Optical coherence tomography in neurodegenerative disorders. ARQUIVOS DE NEURO-PSIQUIATRIA 2022; 80:180-191. [PMID: 35352756 PMCID: PMC9648920 DOI: 10.1590/0004-282x-anp-2021-0134] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 05/21/2021] [Accepted: 06/15/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND Structural imaging of the brain is the most widely used diagnostic tool for investigating neurodegenerative diseases. More advanced structural imaging techniques have been applied to early or prodromic phases, but they are expensive and not widely available. Therefore, it is highly desirable to search for noninvasive, easily accessible, low-cost clinical biomarkers suitable for large-scale population screening, in order to focus on making diagnoses at the earliest stages of the disease. In this scenario, imaging studies focusing on the structures of the retina have increasingly been used for evaluating neurodegenerative diseases. The retina shares embryological, histological, biochemical, microvascular and neurotransmitter similarities with the cerebral cortex, thus making it a uniquely promising biomarker for neurodegenerative diseases. Optical coherence tomography is a modern noninvasive imaging technique that provides high-resolution two-dimensional cross-sectional images and quantitative reproducible three-dimensional volumetric measurements of the optic nerve head and retina. This technology is widely used in ophthalmology practice for diagnosing and following up several eye diseases, such as glaucoma, diabetic retinopathy and age-related macular degeneration. Its clinical impact on neurodegenerative diseases has raised enormous interest over recent years, as several clinical studies have demonstrated that these diseases give rise to reduced thickness of the inner retinal nerve fiber layer, mainly composed of retinal ganglion cells and their axons. In this review, we aimed to address the clinical utility of optical coherence tomography for diagnosing and evaluating different neurodegenerative diseases, to show the potential of this noninvasive and easily accessible method.
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Affiliation(s)
- Leonardo Provetti Cunha
- Universidade Federal de Juiz de Fora, Faculdade de Medicina, Divisão de Oftalmologia, Juiz de Fora MG, Brazil
- Universidade de São Paulo, Faculdade de Medicina, Divisão de Oftalmologia, São Paulo SP, Brazil
- Universidade Federal de Juiz de Fora, Faculdade de Medicina, Pós-Graduação em Saúde, Núcleo de Pesquisa em Neurologia, Juiz de Fora MG, Brazil
| | - Leopoldo Antônio Pires
- Universidade Federal de Juiz de Fora, Faculdade de Medicina, Pós-Graduação em Saúde, Núcleo de Pesquisa em Neurologia, Juiz de Fora MG, Brazil
- Universidade Federal de Juiz de Fora, Hospital Universitário, Serviço de Neurologia, Juiz de Fora MG, Brazil
- Universidade Federal de Juiz de Fora, Hospital Universitário, Serviço de Neurologia, Juiz de Fora MG, Brazil
| | - Marcelo Maroco Cruzeiro
- Universidade Federal de Juiz de Fora, Faculdade de Medicina, Pós-Graduação em Saúde, Núcleo de Pesquisa em Neurologia, Juiz de Fora MG, Brazil
- Universidade Federal de Juiz de Fora, Hospital Universitário, Serviço de Neurologia, Juiz de Fora MG, Brazil
- Universidade Federal de Juiz de Fora, Hospital Universitário, Serviço de Neurologia, Juiz de Fora MG, Brazil
| | - Ana Laura Maciel Almeida
- Universidade Federal de Juiz de Fora, Faculdade de Medicina, Pós-Graduação em Saúde, Núcleo de Pesquisa em Neurologia, Juiz de Fora MG, Brazil
- Universidade Federal de Juiz de Fora, Hospital Universitário, Serviço de Neurologia, Juiz de Fora MG, Brazil
- Universidade Federal de Juiz de Fora, Hospital Universitário, Serviço de Neurologia, Juiz de Fora MG, Brazil
| | - Luiza Cunha Martins
- Universidade Federal de Juiz de Fora, Faculdade de Medicina, Pós-Graduação em Saúde, Núcleo de Pesquisa em Neurologia, Juiz de Fora MG, Brazil
- Universidade Federal de Juiz de Fora, Faculdade de Medicina, Departamento de Clínica Médica, Juiz de Fora MG, Brazil
| | - Pedro Nascimento Martins
- Universidade Federal de Juiz de Fora, Faculdade de Medicina, Pós-Graduação em Saúde, Núcleo de Pesquisa em Neurologia, Juiz de Fora MG, Brazil
- Universidade Federal de Juiz de Fora, Faculdade de Medicina, Departamento de Clínica Médica, Juiz de Fora MG, Brazil
| | - Nadia Shigaeff
- Universidade Federal de Juiz de Fora, Faculdade de Medicina, Pós-Graduação em Saúde, Núcleo de Pesquisa em Neurologia, Juiz de Fora MG, Brazil
- Universidade Federal de Juiz de Fora, Instituto de Ciências Humanas, Departamento de Psicologia, Juiz de Fora MG, Brazil
| | - Thiago Cardoso Vale
- Universidade Federal de Juiz de Fora, Faculdade de Medicina, Pós-Graduação em Saúde, Núcleo de Pesquisa em Neurologia, Juiz de Fora MG, Brazil
- Universidade Federal de Juiz de Fora, Hospital Universitário, Serviço de Neurologia, Juiz de Fora MG, Brazil
- Universidade Federal de Juiz de Fora, Hospital Universitário, Serviço de Neurologia, Juiz de Fora MG, Brazil
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Vadakkan KI. Neurological disorders of COVID-19 can be explained in terms of both "loss and gain of function" states of a solution for the nervous system. Brain Circ 2021; 7:217-222. [PMID: 34667907 PMCID: PMC8459691 DOI: 10.4103/bc.bc_46_21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 07/07/2021] [Accepted: 07/23/2021] [Indexed: 12/14/2022] Open
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Vadakkan KI. Framework for internal sensation of pleasure using constraints from disparate findings in nucleus accumbens. World J Psychiatry 2021; 11:681-695. [PMID: 34733636 PMCID: PMC8546768 DOI: 10.5498/wjp.v11.i10.681] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 06/27/2021] [Accepted: 09/02/2021] [Indexed: 02/06/2023] Open
Abstract
It is necessary to find a mechanism that generates first-person inner sensation of pleasure to understand what causes addiction and associated behaviour by drugs of abuse. The actual mechanism is expected to explain several disparate findings in nucleus accumbens (NAc), a brain region associated with pleasure, in an interconnected manner. Previously, it was possible to derive a mechanism for natural learning and explain: (1) Generation of inner sensation of memory using changes generated by learning; and (2) Long-term potentiation as an experimental delayed scaled-up change by the same mechanism that occur during natural learning. By extending these findings and by using disparate third person observations in NAc from several studies, present work provides a framework of a mechanism that generates internal sensation of pleasure that can provide interconnected explanations for: (1) Ability to induce robust long-term depression (LTD) in NAc from naïve animals; (2) Impaired ability to induce LTD in “addicted” state; (3) Attenuation of postsynaptic potentials by cocaine; and (4) Reduced firing of medium spiny neurons in response to cocaine or dopamine. Findings made by this work are testable.
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Gonçalves PB, Sodero ACR, Cordeiro Y. Green Tea Epigallocatechin-3-gallate (EGCG) Targeting Protein Misfolding in Drug Discovery for Neurodegenerative Diseases. Biomolecules 2021; 11:767. [PMID: 34065606 PMCID: PMC8160836 DOI: 10.3390/biom11050767] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 05/14/2021] [Accepted: 05/16/2021] [Indexed: 12/15/2022] Open
Abstract
The potential to treat neurodegenerative diseases (NDs) of the major bioactive compound of green tea, epigallocatechin-3-gallate (EGCG), is well documented. Numerous findings now suggest that EGCG targets protein misfolding and aggregation, a common cause and pathological mechanism in many NDs. Several studies have shown that EGCG interacts with misfolded proteins such as amyloid beta-peptide (Aβ), linked to Alzheimer's disease (AD), and α-synuclein, linked to Parkinson's disease (PD). To date, NDs constitute a serious public health problem, causing a financial burden for health care systems worldwide. Although current treatments provide symptomatic relief, they do not stop or even slow the progression of these devastating disorders. Therefore, there is an urgent need to develop effective drugs for these incurable ailments. It is expected that targeting protein misfolding can serve as a therapeutic strategy for many NDs since protein misfolding is a common cause of neurodegeneration. In this context, EGCG may offer great potential opportunities in drug discovery for NDs. Therefore, this review critically discusses the role of EGCG in NDs drug discovery and provides updated information on the scientific evidence that EGCG can potentially be used to treat many of these fatal brain disorders.
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Affiliation(s)
| | | | - Yraima Cordeiro
- Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro 21949-900, Brazil; (P.B.G.); (A.C.R.S.)
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Viegas C, Fraga CAM, Sousa ME, Tarozzi A. Editorial: Oxidative Stress: How Has It Been Considered in the Design of New Drug Candidates for Neurodegenerative Diseases? Front Pharmacol 2020; 11:609274. [PMID: 33362563 PMCID: PMC7756109 DOI: 10.3389/fphar.2020.609274] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Accepted: 10/05/2020] [Indexed: 12/18/2022] Open
Affiliation(s)
- Claudio Viegas
- Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | | | - Maria Emilia Sousa
- Department for Life Quality Studies, University of Bologna, Bologna, Italy
| | - Andrea Tarozzi
- Laboratory of Research in Medicinal Chemistry (PeQuiM), Federal University of Alfenas, Alfenas, Brazil
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8
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Guzik-Makaruk EM, Pływaczewski EW, Laskowska K, Filipkowski W, Jurgielewicz-Delegacz E, Mroczko P. A Comparative Analysis of the Treatment of Decision-Making by or for Patients with Neurodegenerative Diseases in Four Legal Jurisdictions. J Alzheimers Dis 2020; 70:1-10. [PMID: 31127787 DOI: 10.3233/jad-190259] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Dementia is associated with the gradual impairment of mental ability. The population of people suffering from dementia is as large as 50 million. Most dementia cases result from various neurodegenerative diseases (NDs) linked by a progressive degeneration of neurons. Among NDs, Alzheimer's disease (AD) is the most frequent cause of dementia and accounts for 60- 80% of cases. Certain pathological changes on the cellular and subcellular level occur even 15 years before the manifestation of clinical symptoms of AD. This first asymptomatic phase of AD is considered a preclinical stage, whereas mild cognitive impairment (MCI) is the symptomatic pre-dementia stage. The third, fully symptomatic phase of AD is dementia due to AD. The presence of specific proteins in the cerebrospinal fluid (CSF) may be considered as a characteristic feature of some NDs. The measurement of their CSF concentrations, together with neuropsychological examination and neuroimaging, may be useful for diagnosing AD. The collection of CSF samples is performed by lumbar puncture, which is a medical procedure that requires obtaining informed consent from patients. While asymptomatic AD patients have full legal capacity, those with dementia require a legal guardian who will represent them. Thus, the objective of this study is to compare the legal systems regulating the legal capacity issue in the USA, U.K. (England and Wales), Germany, and Poland. These countries have been chosen as examples of three different types of legal orders, according to the sources of law, i.e., civil law, common law, and case law.
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Affiliation(s)
- Ewa M Guzik-Makaruk
- Department of Criminal Law and Criminology, Faculty of Law, University of Białystok, Poland
| | - Emil W Pływaczewski
- Department of Criminal Law and Criminology, Faculty of Law, University of Białystok, Poland
| | - Katarzyna Laskowska
- Department of Criminal Law and Criminology, Faculty of Law, University of Białystok, Poland
| | - Wojciech Filipkowski
- Department of Criminal Law and Criminology, Faculty of Law, University of Białystok, Poland
| | | | - Piotr Mroczko
- Department of Criminal Law and Criminology, Faculty of Law, University of Białystok, Poland
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Carradori D, Labrak Y, Miron VE, Saulnier P, Eyer J, Préat V, des Rieux A. Retinoic acid-loaded NFL-lipid nanocapsules promote oligodendrogenesis in focal white matter lesion. Biomaterials 2020; 230:119653. [DOI: 10.1016/j.biomaterials.2019.119653] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Revised: 11/15/2019] [Accepted: 11/24/2019] [Indexed: 02/08/2023]
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Vadakkan KI. From cells to sensations: A window to the physics of mind. Phys Life Rev 2019; 31:44-78. [PMID: 31759872 DOI: 10.1016/j.plrev.2019.10.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Revised: 09/06/2019] [Accepted: 10/16/2019] [Indexed: 12/14/2022]
Abstract
Principles of methods for studying particles and fields that cannot be sensed by third-person observers by routine methods can be used to understand the physics of first-person properties of mind. Accordingly, whenever a system exhibits disparate features at multiple levels, unique combination of constraints offered by them direct us towards a solution that will be the first principle of that system. Using this method, it was possible to arrive at a third-person observable solution-point of brain-mind interface. Examination of this location identified a set of unique features that can allow an associatively learned (cue) stimulus to spark hallucinations that form units of first-person internal (inner) sensations reminiscent of stimuli from the associatively learned second item in timescales of milliseconds. It allows us to peep into a virtual space of mind where different modifications and integrations of units of internal sensations generate their different net conformations ranging from perception to an inner sense of hidden relationships that form a hypothesis. Since sparking of inner sensations of the late arriving (when far away) or non-arriving (when hidden) features of items started providing survival advantage, the focus of evolution might have been to optimize this property. Hence, the circuity that generates it can be considered as the primary circuitry of the system. The solution provides several testable predictions. By taking readers through the process of deriving the solution and by explaining how it interconnects disparate findings, it is hoped that the factors determining the physics of mind will become evident.
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Affiliation(s)
- Kunjumon I Vadakkan
- Division of Neurology, Department of Medicine, QEII Health Sciences Centre, 1796 Summer Street, Dalhousie University, Halifax, NS, B3H 3A7, Canada.
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da S. Hage-Melim LI, Ferreira JV, de Oliveira NK, Correia LC, Almeida MR, Poiani JG, Taft CA, de Paula da Silva CH. The Impact of Natural Compounds on the Treatment of Neurodegenerative Diseases. CURR ORG CHEM 2019. [DOI: 10.2174/1385272823666190327100418] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Neurodegenerative diseases (NDDs) are characterized by a progressive deterioration of the motor and/or cognitive function, that are often accompanied by psychiatric disorders, caused by a selective loss of neurons in the central nervous system. Among the NDDs we can mention Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), spinocerebellar ataxia 3 (SCA3), spinal and bulbar muscular atrophy (SBMA) and Creutzfeldt-Jakob disease (CJD). AD and HD are characterized mainly by massive neuronal loss. PD, ALS, SCA3 and SBMA are agerelated diseases which have characteristic motor symptoms. CJD is an NDD caused by prion proteins. With increasing life expectancy, elderly populations tend to have more health problems, such as chronic diseases related to age and disability. Therefore, the development of therapeutic strategies to treat or prevent multiple pathophysiological conditions in the elderly can improve the expectation and quality of life. The attention of researchers has been focused on bioactive natural compounds that represent important resources in the discovery and development of drug candidates against NDDs. In this review, we discuss the pathogenesis, symptoms, potential targets, treatment and natural compounds effective in the treatment of AD, PD, HD, ALS, SCA3, SBMA and CJD.
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Affiliation(s)
- Lorane I. da S. Hage-Melim
- Laboratorio de Quimica Farmaceutica e Medicinal (PharMedChem), Universidade Federal do Amapa, Macapa, Brazil
| | - Jaderson V. Ferreira
- Laboratorio de Quimica Farmaceutica e Medicinal (PharMedChem), Universidade Federal do Amapa, Macapa, Brazil
| | - Nayana K.S. de Oliveira
- Laboratorio de Quimica Farmaceutica e Medicinal (PharMedChem), Universidade Federal do Amapa, Macapa, Brazil
| | - Lenir C. Correia
- Laboratorio de Quimica Farmaceutica e Medicinal (PharMedChem), Universidade Federal do Amapa, Macapa, Brazil
| | - Marcos R.S. Almeida
- Laboratorio de Quimica Farmaceutica e Medicinal (PharMedChem), Universidade Federal do Amapa, Macapa, Brazil
| | - João G.C. Poiani
- Laboratorio Computacional de Química Farmaceutica, Departamento de Ciencias Farmaceuticas, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil
| | - Carlton A. Taft
- Centro Brasileiro de Pesquisas Fisicas, Rio de Janeiro, Rio de Janeiro, Brazil
| | - Carlos H.T. de Paula da Silva
- Laboratorio Computacional de Química Farmaceutica, Departamento de Ciencias Farmaceuticas, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil
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Hussain R, Zubair H, Pursell S, Shahab M. Neurodegenerative Diseases: Regenerative Mechanisms and Novel Therapeutic Approaches. Brain Sci 2018; 8:E177. [PMID: 30223579 PMCID: PMC6162719 DOI: 10.3390/brainsci8090177] [Citation(s) in RCA: 139] [Impact Index Per Article: 19.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Revised: 09/03/2018] [Accepted: 09/12/2018] [Indexed: 12/12/2022] Open
Abstract
Regeneration refers to regrowth of tissue in the central nervous system. It includes generation of new neurons, glia, myelin, and synapses, as well as the regaining of essential functions: sensory, motor, emotional and cognitive abilities. Unfortunately, regeneration within the nervous system is very slow compared to other body systems. This relative slowness is attributed to increased vulnerability to irreversible cellular insults and the loss of function due to the very long lifespan of neurons, the stretch of cells and cytoplasm over several dozens of inches throughout the body, insufficiency of the tissue-level waste removal system, and minimal neural cell proliferation/self-renewal capacity. In this context, the current review summarized the most common features of major neurodegenerative disorders; their causes and consequences and proposed novel therapeutic approaches.
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Affiliation(s)
- Rashad Hussain
- Center for Translational Neuromedicine, University of Rochester, NY 14642, USA.
| | - Hira Zubair
- Department of Animal Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan.
| | - Sarah Pursell
- Center for Translational Neuromedicine, University of Rochester, NY 14642, USA.
| | - Muhammad Shahab
- Department of Animal Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan.
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Wilkaniec A, Gąssowska M, Czapski GA, Cieślik M, Sulkowski G, Adamczyk A. P2X7 receptor-pannexin 1 interaction mediates extracellular alpha-synuclein-induced ATP release in neuroblastoma SH-SY5Y cells. Purinergic Signal 2017; 13:347-361. [PMID: 28516276 PMCID: PMC5563296 DOI: 10.1007/s11302-017-9567-2] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Accepted: 04/30/2017] [Indexed: 12/14/2022] Open
Abstract
Abnormalities of alpha-synuclein (ASN), the main component of protein deposits (Lewy bodies), were observed in Parkinson’s disease (PD), dementia with Lewy bodies, Alzheimer’s disease, and other neurodegenerative disorders. These alterations include increase in the levels of soluble ASN oligomers in the extracellular space. Numerous works have identified several mechanisms of their toxicity, including stimulation of the microglial P2X7 receptor leading to oxidative stress. While the significant role of purinergic signaling—particularly, P2 family receptors—in neurodegenerative disorders is well known, the interaction of extracellular soluble ASN with neuronal purinergic receptors is yet to be studied. Therefore, in this study, we have investigated the effect of ASN on P2 purinergic receptors and ATP-dependent signaling. We used neuroblastoma SH-SY5Y cell line and rat synaptoneurosomes treated with exogenous soluble ASN. The experiments were performed using spectrofluorometric, radiochemical, and immunochemical methods. We found the following: (i) ASN-induced intracellular free calcium mobilization in neuronal cells and nerve endings depends on the activation of purinergic P2X7 receptors; (ii) activation of P2X7 receptors leads to pannexin 1 recruitment to form an active complex responsible for ATP release; and (iii) ASN greatly decreases the activity of extracellular ecto-ATPase responsible for ATP degradation. Thus, it is concluded that purinergic receptors might be putative pharmacological targets in the molecular mechanism of extracellular ASN toxicity. Interference with P2X7 signaling seems to be a promising strategy for the prevention or therapy of PD and other neurodegenerative disorders.
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Affiliation(s)
- Anna Wilkaniec
- Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5 St., 02-106, Warsaw, Poland.
| | - Magdalena Gąssowska
- Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5 St., 02-106, Warsaw, Poland
| | - Grzegorz A Czapski
- Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5 St., 02-106, Warsaw, Poland
| | - Magdalena Cieślik
- Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5 St., 02-106, Warsaw, Poland
| | - Grzegorz Sulkowski
- Department of Neurochemistry, Laboratory of Pathoneurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5 St., 02-106, Warsaw, Poland
| | - Agata Adamczyk
- Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5 St., 02-106, Warsaw, Poland
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