Pub Date : 2023-01-01DOI: 10.23937/2643-4539/1710025
Blanco-Lezcano Lisette, González-Fraguela María Elena, de Larrea Guadalupe Zaldívar-Lelo, Pérez-Serrano Rosa Martha, Frade-Pérez María Daniela, Serrano-Sánchez Teresa, Turner Liliana Francis
{"title":"Medium-Term Effect of Pedunculopontine Nucleus Neurotoxic Lesion on Motor Function and Gene Expression of Protein Related to Dopaminergic Homeostasis in Rat","authors":"Blanco-Lezcano Lisette, González-Fraguela María Elena, de Larrea Guadalupe Zaldívar-Lelo, Pérez-Serrano Rosa Martha, Frade-Pérez María Daniela, Serrano-Sánchez Teresa, Turner Liliana Francis","doi":"10.23937/2643-4539/1710025","DOIUrl":"https://doi.org/10.23937/2643-4539/1710025","url":null,"abstract":"","PeriodicalId":92384,"journal":{"name":"International journal of neurodegenerative disorders","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68754667","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}
Pub Date : 2022-12-31DOI: 10.23937/2643-4539/1710023
R. Mohammed
Down syndrome (DS) is the most frequent genetic disease characterized by several neuropathological features including alteration in neurogenesis, mental disability, cognitive impairments, learning-memory deficits and early onset of Alzheimer’s disease (AD). Over expression of chromosome 21 genes, localized in Down Syndrome Critical Region (DSCR), is the main cause of DS neuropathological features. We studied herein one of DSCR genes, DYRK1A (Dual-Specificity Tyrosine-Phosphorylation-Regulated Ki nase 1A), well-known Drosophila Mini-Brain gene, as a master regulator involved in DS neuropathological features and associated AD. DYRK1A is a central member of phosphorylation pathways regulating cell cycle and belongs to a family of Dual-Specificity Protein Kinases (DYRK kinases) playing key roles in central nervous system. DYRK1A regulates several transcriptional factors, such as CREB (cyclic-AMP response element-binding protein), NFAT (nuclear factor of activated T cells) and signaling pathways playing critical roles in brain functions. Significant associations were found between DYRK1A and regulation of cytoskeletal dynamics of actin, tubulin or microtubule-linked protein Tau, regulation of Tau phosphorylation, Amyloid Precursor Protein (APP) or Presenilin 1 (PS1), regulation of neurogenesis, synaptogenesis, and AD-like neurofibrillary tangles formation. Interestingly, normalization of DYRK1A overexpression by DYRK1A inhibitor, epigalloctechin-3-gallate (EGCG), rescues brain defects, restores cognitive impairments in DS trisomic and DYRK1A transgenic mouse models and DS patients,modulates Amyloid Precursor Protein (APP) cleavage and reduces cerebral amyloidosis in AD transgenic mouse models. DYRK1A inhibitors such as Har-mine, LeucettineL41, SM07883 successfully reduces Tau phosphorylation at multiple AD-related sites, rescues AD phenotypes in APP/PS1 mice and correct cognitive and memory deficits in AD animal models. These results indica tes DYRK1A inhibitors as effective treatments and identifies DYRK1A as a master regulatory protein involved in DS and AD neuropathological features suggestingDYRK1A as promising potential drug target for therapeutics and treatments of DS and AD. Down syndrome, Alzheimer’s disease, Mouse genetic models, Brain abnormalities, Cognitive deficits, Mental disabili -ty, DYRK1A inhibitors, DYRK1A therapeutic target
{"title":"Dual‐Specificity Tyrosine Phosphorylation‐Regulated Kinase‐1A (DYRK1A), A Master Regulatory Protein Involved in Down Syndrome Brain Alterations and Mental Disability, A Key Contributor to Neurodegenerative Disorders of Alzheimer's Disease and A Potential Therapeutic Target","authors":"R. Mohammed","doi":"10.23937/2643-4539/1710023","DOIUrl":"https://doi.org/10.23937/2643-4539/1710023","url":null,"abstract":"Down syndrome (DS) is the most frequent genetic disease characterized by several neuropathological features including alteration in neurogenesis, mental disability, cognitive impairments, learning-memory deficits and early onset of Alzheimer’s disease (AD). Over expression of chromosome 21 genes, localized in Down Syndrome Critical Region (DSCR), is the main cause of DS neuropathological features. We studied herein one of DSCR genes, DYRK1A (Dual-Specificity Tyrosine-Phosphorylation-Regulated Ki nase 1A), well-known Drosophila Mini-Brain gene, as a master regulator involved in DS neuropathological features and associated AD. DYRK1A is a central member of phosphorylation pathways regulating cell cycle and belongs to a family of Dual-Specificity Protein Kinases (DYRK kinases) playing key roles in central nervous system. DYRK1A regulates several transcriptional factors, such as CREB (cyclic-AMP response element-binding protein), NFAT (nuclear factor of activated T cells) and signaling pathways playing critical roles in brain functions. Significant associations were found between DYRK1A and regulation of cytoskeletal dynamics of actin, tubulin or microtubule-linked protein Tau, regulation of Tau phosphorylation, Amyloid Precursor Protein (APP) or Presenilin 1 (PS1), regulation of neurogenesis, synaptogenesis, and AD-like neurofibrillary tangles formation. Interestingly, normalization of DYRK1A overexpression by DYRK1A inhibitor, epigalloctechin-3-gallate (EGCG), rescues brain defects, restores cognitive impairments in DS trisomic and DYRK1A transgenic mouse models and DS patients,modulates Amyloid Precursor Protein (APP) cleavage and reduces cerebral amyloidosis in AD transgenic mouse models. DYRK1A inhibitors such as Har-mine, LeucettineL41, SM07883 successfully reduces Tau phosphorylation at multiple AD-related sites, rescues AD phenotypes in APP/PS1 mice and correct cognitive and memory deficits in AD animal models. These results indica tes DYRK1A inhibitors as effective treatments and identifies DYRK1A as a master regulatory protein involved in DS and AD neuropathological features suggestingDYRK1A as promising potential drug target for therapeutics and treatments of DS and AD. Down syndrome, Alzheimer’s disease, Mouse genetic models, Brain abnormalities, Cognitive deficits, Mental disabili -ty, DYRK1A inhibitors, DYRK1A therapeutic target","PeriodicalId":92384,"journal":{"name":"International journal of neurodegenerative disorders","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44237213","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":"Similarities among Alzheimer's Disease, Parkinson's Disease and Dementia may Call for a Similar Treatment","authors":"Chakraborty Ashok, Diwan Anil","doi":"10.36959/459/608","DOIUrl":"https://doi.org/10.36959/459/608","url":null,"abstract":"","PeriodicalId":92384,"journal":{"name":"International journal of neurodegenerative disorders","volume":"114 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77703187","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}
Pub Date : 2022-03-30DOI: 10.23937/2643-4539/1710022
Brown Katherine A, Summers Dale KL, Spencer Kristie A
{"title":"Cognitive Decline in Parkinson's Disease: Theories and Implications for Rehabilitation","authors":"Brown Katherine A, Summers Dale KL, Spencer Kristie A","doi":"10.23937/2643-4539/1710022","DOIUrl":"https://doi.org/10.23937/2643-4539/1710022","url":null,"abstract":"","PeriodicalId":92384,"journal":{"name":"International journal of neurodegenerative disorders","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48064869","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}
Neurodegeneration with brain iron accumulation (NBIA) comprises a group of rare but devastating inherited neurological diseases with unifying features of gradual cognitive and motor decline, and progressive degeneration of basal ganglia, globus pallidus, and reticular part of substantia nigra, produced by brain iron accumulation [1]. The most common disorders presented in infancy and childhood are Betapropeller Protein‐Associated Neurodegeneration, Pantothenate Kinase‐ Associated Neurodegeneration, PhosphoLipase A2‐Associated Neurodegeneration, and Mitochondrial membrane Protein‐ Associated Neurodegeneration [2].
脑铁积累性神经变性(Neurodegeneration with brain iron accumulation, NBIA)是一组罕见但具有破坏性的遗传性神经系统疾病，其共同特征是脑铁积累导致认知和运动能力逐渐下降，基底节、苍白球和黑质网状部分进行性变性[1]。婴儿期和儿童期最常见的疾病是β -螺旋桨蛋白相关神经变性、泛酸激酶相关神经变性、磷脂酶A2相关神经变性和线粒体膜蛋白相关神经变性[2]。
{"title":"Deep Brain Stimulation or Pallidotomy for Dystonia in Neurodegeneration with Brain Iron Accumulation? A Call for Justice To the Balance","authors":"Guach‑Hevia David Armando","doi":"10.36959/459/609","DOIUrl":"https://doi.org/10.36959/459/609","url":null,"abstract":"Neurodegeneration with brain iron accumulation (NBIA) comprises a group of rare but devastating inherited neurological diseases with unifying features of gradual cognitive and motor decline, and progressive degeneration of basal ganglia, globus pallidus, and reticular part of substantia nigra, produced by brain iron accumulation [1]. The most common disorders presented in infancy and childhood are Betapropeller Protein‐Associated Neurodegeneration, Pantothenate Kinase‐ Associated Neurodegeneration, PhosphoLipase A2‐Associated Neurodegeneration, and Mitochondrial membrane Protein‐ Associated Neurodegeneration [2].","PeriodicalId":92384,"journal":{"name":"International journal of neurodegenerative disorders","volume":"76 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90296479","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}
Pub Date : 2021-09-10DOI: 10.23937/2643-4539/1710021
Ashraf Rajab
{"title":"Attitudes Toward People with Epilepsy in Libya, the Conundrum Continues!","authors":"Ashraf Rajab","doi":"10.23937/2643-4539/1710021","DOIUrl":"https://doi.org/10.23937/2643-4539/1710021","url":null,"abstract":"","PeriodicalId":92384,"journal":{"name":"International journal of neurodegenerative disorders","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43360346","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}
Pub Date : 2021-05-08DOI: 10.23937/2643-4539/1710019
Kochman Eliyahu M, Akhtar Kainat, Dr. Aleem Ali, Shin Damian S
Parkinson’s disease (PD) is the second most common neurodegenerative disease, presenting with the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and motor symptoms. Categorized as a synucleinopathy, the pathological hallmark of PD is intracellular filamentous Lewy bodies (LB), which are formed from protopathic aggregates. The most prevalent of these proteins is the presynaptic protein ɑ-synuclein (α-syn). While commonly attributed to neuronal death in SNpc, postmortem studies have shown α-syn immunoreactivity and LB pathology in the peripheral, central, and enteric nervous system (ENS). While the etiology of misfolded α-syn is unknown, various gut microbiota and substrates are associated with α-syn dysfunction. Gastrointestinal (GI) dysfunction, a common feature in the prodromal phase of PD patients, and histological evidence have led to the Braak hypothesis of misfolded α-syn commencement in the ENS and propagation to brainstem nuclei including the SNpc via the vagus nerve. Altered or stressed gut environment is thought to contribute to the misfolding of α-syn that subsequently initiates or spurs its propagation from the gut myenteric plexus. This review covers clinical and pre-clinical evidence of the involvement of enteric α-syn in PD related to GI dysfunction and brain pathology.
{"title":"Clinical and Pre-Clinical Evidence for Enteric α-Synuclein Involvement in Parkinson's Disease","authors":"Kochman Eliyahu M, Akhtar Kainat, Dr. Aleem Ali, Shin Damian S","doi":"10.23937/2643-4539/1710019","DOIUrl":"https://doi.org/10.23937/2643-4539/1710019","url":null,"abstract":"Parkinson’s disease (PD) is the second most common neurodegenerative disease, presenting with the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and motor symptoms. Categorized as a synucleinopathy, the pathological hallmark of PD is intracellular filamentous Lewy bodies (LB), which are formed from protopathic aggregates. The most prevalent of these proteins is the presynaptic protein ɑ-synuclein (α-syn). While commonly attributed to neuronal death in SNpc, postmortem studies have shown α-syn immunoreactivity and LB pathology in the peripheral, central, and enteric nervous system (ENS). While the etiology of misfolded α-syn is unknown, various gut microbiota and substrates are associated with α-syn dysfunction. Gastrointestinal (GI) dysfunction, a common feature in the prodromal phase of PD patients, and histological evidence have led to the Braak hypothesis of misfolded α-syn commencement in the ENS and propagation to brainstem nuclei including the SNpc via the vagus nerve. Altered or stressed gut environment is thought to contribute to the misfolding of α-syn that subsequently initiates or spurs its propagation from the gut myenteric plexus. This review covers clinical and pre-clinical evidence of the involvement of enteric α-syn in PD related to GI dysfunction and brain pathology.","PeriodicalId":92384,"journal":{"name":"International journal of neurodegenerative disorders","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43744263","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}
Fothergill-Misbah Natasha, Dotchin Catherine, Kisima John, H. Kate, Walker Richard
Background: Parkinson’s disease (PD) is a debilitating neurological disease that can result in a reduced quality of life for people with Parkinson’s disease (PwP) and their families. The incidence of PD continues to increase as the global population ages, as is being experienced in Tanzania and much of sub-Saharan Africa, yet healthcare systems are under-developed and not prepared to manage the burden posed by chronic conditions. Little is known about people’s experiences of long-term drug treatment for PD and the impact disease progression has on PwP and their families’ lives. This paper outlines findings from a small-scale qualitative research study on the experiences of PwP in later stages of illness and their families in the Hai district of Tanzania. Methods: Semi-structured biographical in-depth interviews were conducted with three PwP and six caregivers in the Hai district of Tanzania. Interviews explored participants’ experiences of living with PD and caring for a family member with PD, their response to biomedical treatment, use of alternative treatment practices and understanding about the disease. Results: PWP and caregivers all expressed the emotional, social, physical and economic strain of PD. PwP felt angry and frustrated with their deteriorating condition and increasing dependence but pleased with the treatment. Caregivers described the full-on nature of their caring role which resulted in increasing social isolation, worry and stress as the PwPs’ condition progressed. Religion, faith and prayers played a significant role in disease management in combination with pharmaceutical treatment. Participants did not report any stigmatisation towards PwP from communities. Conclusion: This study outlines the emotional, financial and physical challenges that PwP at advanced disease stages and their caregivers experienced in the Hai district. It highlights the need for PD management to acknowledge the role of spiritual healing and social support in combination with biomedical treatment to achieve effective care and improve the wellbeing of PwP and their families, and the need for increased awareness and understanding about PD in the region.
{"title":"The Experience of Parkinson's Disease in Hai District, Tanzania","authors":"Fothergill-Misbah Natasha, Dotchin Catherine, Kisima John, H. Kate, Walker Richard","doi":"10.36959/459/606","DOIUrl":"https://doi.org/10.36959/459/606","url":null,"abstract":"Background: Parkinson’s disease (PD) is a debilitating neurological disease that can result in a reduced quality of life for people with Parkinson’s disease (PwP) and their families. The incidence of PD continues to increase as the global population ages, as is being experienced in Tanzania and much of sub-Saharan Africa, yet healthcare systems are under-developed and not prepared to manage the burden posed by chronic conditions. Little is known about people’s experiences of long-term drug treatment for PD and the impact disease progression has on PwP and their families’ lives. This paper outlines findings from a small-scale qualitative research study on the experiences of PwP in later stages of illness and their families in the Hai district of Tanzania. Methods: Semi-structured biographical in-depth interviews were conducted with three PwP and six caregivers in the Hai district of Tanzania. Interviews explored participants’ experiences of living with PD and caring for a family member with PD, their response to biomedical treatment, use of alternative treatment practices and understanding about the disease. Results: PWP and caregivers all expressed the emotional, social, physical and economic strain of PD. PwP felt angry and frustrated with their deteriorating condition and increasing dependence but pleased with the treatment. Caregivers described the full-on nature of their caring role which resulted in increasing social isolation, worry and stress as the PwPs’ condition progressed. Religion, faith and prayers played a significant role in disease management in combination with pharmaceutical treatment. Participants did not report any stigmatisation towards PwP from communities. Conclusion: This study outlines the emotional, financial and physical challenges that PwP at advanced disease stages and their caregivers experienced in the Hai district. It highlights the need for PD management to acknowledge the role of spiritual healing and social support in combination with biomedical treatment to achieve effective care and improve the wellbeing of PwP and their families, and the need for increased awareness and understanding about PD in the region.","PeriodicalId":92384,"journal":{"name":"International journal of neurodegenerative disorders","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88182041","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}
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