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1.
Artigo em Coreano | WPRIM (Pacífico Ocidental) | ID: wprim-787397

RESUMO

Dementia with Lewy bodies(DLB) is the second most common neurodegenerative disease. However, DLB might not be adequately diagnosed due to its variety of clinical symptoms. The authors present 65-year-old Mrs. A. who showed Parkinson's movement, cognitive decline, psychological symptoms, and autonomic dysfunction. According to the clinical features and biological markers in the recently revised DLB criteria, Mrs. A. was diagnosed with probable DLB. Differential diagnoses of delirium, Parkinson's dementia, and Alzheimer's dementia were discussed. Psychopharmacological treatments of antidepressants or anxiolytics caused intolerable side effects and showed little efficacy to Mrs. A. She experienced two episodes of hyponatremia during her one-year treatment. Recovery from neurological symptoms due to the first hyponatremia was time-consuming, and in the second, it was associated with changes in the level of consciousness despite relatively mild hyponatremia. A fall that occurred in the latter part of treatment triggered remarkable deterioration of DLB symptoms and daily life function. Prevention of falls is important for maintaining the quality of life of patients with DLB.


Assuntos
Acidentes por Quedas , Idoso , alfa-Sinucleína , Ansiolíticos , Antidepressivos , Biomarcadores , Estado de Consciência , Delírio , Demência , Diagnóstico , Diagnóstico Diferencial , Humanos , Hiponatremia , Corpos de Lewy , Doenças Neurodegenerativas , Qualidade de Vida
2.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-765866

RESUMO

The aggregation of α-synuclein (α-syn) has been implicated in the pathogenesis of many neurodegenerative disorders, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Postmortem analyses of α-syn pathology, especially that of PD, have suggested that aggregates progressively spread from a few discrete locations to wider brain regions. The neuron-to-neuron propagation of α-syn has been suggested to be the underlying mechanism by which aggregates spread throughout the brain. Many cellular and animal models has been created to study cell-to-cell propagation. Recently, it has been shown that a single injection of preformed fibrils (PFFs) made of recombinant α-syn proteins into various tissues and organs of many different animal species results in widespread α-syn pathology in the central nervous system (CNS). These PFF models have been extensively used to study the mechanism by which aggregates spread throughout the brain. Here, we review what we have learned from PFF models, describe the nature of PFFs and the neuropathological features, neurophysiological characteristics, and behavioral outcomes of the models.


Assuntos
alfa-Sinucleína , Animais , Encéfalo , Sistema Nervoso Central , Demência , Corpos de Lewy , Modelos Animais , Atrofia de Múltiplos Sistemas , Doenças Neurodegenerativas , Doença de Parkinson , Patologia
3.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-765840

RESUMO

OBJECTIVE: To clarify the specificity of the ‘hot cross bun’ sign (HCBS) for multiple system atrophy (MSA) in adult cerebellar ataxia or parkinsonism. METHODS: The radiologic information systems at an academic center and affiliated veterans' hospital were queried using the keywords ‘hot cross bun,’ ‘pontocerebellar,’ ‘cruciate,’ ‘cruciform,’ ‘MSA,’ ‘multiple system atrophy,’ and ‘multisystem atrophy.’ Scans were reviewed by a neurologist and neuroradiologist to identify the HCBS. Subjects with the HCBS were reviewed by 2 neurologists to identify the most likely etiology of the patient's neurologic symptoms. RESULTS: Eleven cases were identified. Etiologies included MSA (4 probable, 2 possible), hereditary cerebellar ataxia (3/11), probable dementia with Lewy bodies (1/11), and uncertain despite autopsy (1/11). CONCLUSION: MSA was the most common etiology. However, 5 of the 11 patients did not have MSA. The most common alternate etiology was an undefined hereditary cerebellar ataxia (3/11).


Assuntos
Adulto , Autopsia , Ataxia Cerebelar , Demência , Hexaclorobenzeno , Humanos , Corpos de Lewy , Imagem por Ressonância Magnética , Atrofia de Múltiplos Sistemas , Manifestações Neurológicas , Atrofias Olivopontocerebelares , Transtornos Parkinsonianos , Sistemas de Informação em Radiologia , Sensibilidade e Especificidade
4.
Experimental Neurobiology ; : 547-553, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-763791

RESUMO

Synucleinopathies are neurodegenerative disorders characterized by the progressive accumulation of α-synuclein (α-syn) in neurons and glia and include Parkinson's disease (PD) and dementia with Lewy bodies (DLB). In this review, we consolidate our key findings and recent studies concerning the role of Toll-like receptor 2 (TLR2), a pattern recognition innate immune receptor, in the pathogenesis of synucleinopathies. First, we address the pathological interaction of α-syn with microglial TLR2 and its neurotoxic inflammatory effects. Then, we show that neuronal TLR2 activation not only induces abnormal α-syn accumulation by impairing autophagy, but also modulates α-syn transmission. Finally, we demonstrate that administration of a TLR2 functional inhibitor improves the neuropathology and behavioral deficits of a synucleinopathy mouse model. Altogether, we present TLR2 modulation as a promising immunotherapy for synucleinopathies.


Assuntos
Animais , Autofagia , Demência , Imunoterapia , Corpos de Lewy , Camundongos , Doenças Neurodegenerativas , Neuroglia , Neurônios , Neuropatologia , Doença de Parkinson , Receptor 2 Toll-Like , Receptores Toll-Like
5.
Experimental Neurobiology ; : 504-515, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-763777

RESUMO

Parkinson’s disease (PD) is one of the late-onset neurodegenerative movement disorder. Major pathological markers of PD include progressive loss of dopaminergic neurons, Lewy body formation, genetic mutations, and environmental factors. Epigenetic regulation of specific gene expression via impaired histone acetylation is associated with neuronal dysfunction in various neurodegenerative diseases. In this study, we hypothesized that histone deacetylase (HDAC) inhibitor, valproic acid (VPA), can improve motor function by enhancing cell survival in PD genetic model mice with LRRK2 R1441G mutation. To address this question, we administered VPA in LRRK2 R1441G transgenic mice to determine whether VPA affects 1) histone acetylation and HDAC expression, 2) dopaminergic neuron survival, 3) inflammatory responses, 4) motor or non-motor symptoms. As results, VPA administration increased histone acetylation level and the number of tyrosine hydroxylase (TH) positive neurons in substantia nigra of LRRK2 R1441G mice. VPA reduced iba-1 positive activated microglia and the mRNA levels of pro-inflammatory marker genes in LRRK2 R1441G mice. In addition, VPA induced the improvement of PD-like motor and non-motor behavior in LRRK2 R1441G mice. These data suggest that the inhibition of HDAC can be further studied as potential future therapeutics for PD.


Assuntos
Acetilação , Animais , Sobrevivência Celular , Neurônios Dopaminérgicos , Epigenômica , Expressão Gênica , Histona Desacetilases , Histonas , Corpos de Lewy , Camundongos , Camundongos Transgênicos , Microglia , Modelos Genéticos , Transtornos dos Movimentos , Doenças Neurodegenerativas , Neurônios , Neuroproteção , RNA Mensageiro , Substância Negra , Tirosina 3-Mono-Oxigenase , Ácido Valproico
6.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-763298

RESUMO

OBJECTIVES: Parkinson disease (PD) is frequently associated with olfactory disorder at early stage, which is caused by deposition of Lewy bodies emerging from the olfactory bulb to higher olfactory centers. Early detection of olfactory disorder in the patients with PD may lead to the early diagnosis and treatment for this refractory disease. METHODS: Visual analog scale (VAS), Jet Stream Olfactometry, and Japanese smell identification test, Open Essence (OE), were carried out on 39 patients with PD. Thirty-one patients with postviral olfactory disorder (PVOD), which was caused by the olfactory mucosal dysfunction, were also enrolled in this study as control. RESULTS: There were no significant differences in detection thresholds (2.2 vs. 1.4, P=0.13), recognition thresholds (3.9 vs. 3.5, P=0.39) and OE (4.8 vs. 4.2, P=0.47) between PVOD and PD, while VAS scores of PVOD and PD were significantly different (2.0 and 6.2, P<0.01). In OE, significant differences were observed in the accuracy rates of menthol (68% vs. 44%, P=0.04) and Indian ink (42% vs. 15%, P=0.01) between PVOD and PD. Of particular interest, patients with PVOD tended to select “no detectable,” while patients with PD tended to select wrong alternative other than “no smell detected.” CONCLUSION: Discrepancy between VAS and OE, and high selected rates of wrong alternative other than “undetectable” in OE might be significant signs of olfactory dysfunction associated with PD.


Assuntos
Grupo com Ancestrais do Continente Asiático , Diagnóstico Precoce , Humanos , Tinta , Corpos de Lewy , Mentol , Olfatometria , Bulbo Olfatório , Doença de Parkinson , Rios , Olfato , Escala Visual Analógica
7.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-765815

RESUMO

In recent years, several radiotracers that selectively bind to pathological tau proteins have been developed. Evidence is emerging that binding patterns of in vivo tau positron emission tomography (PET) studies in Alzheimer's disease (AD) patients closely resemble the distribution patterns of known neurofibrillary tangle pathology, with the extent of tracer binding reflecting the clinical and pathological progression of AD. In Lewy body diseases (LBD), tau PET imaging has clearly revealed cortical tau burden with a distribution pattern distinct from AD and increased cortical binding within the LBD spectrum. In progressive supranuclear palsy, the globus pallidus and midbrain have shown increased binding most prominently. Tau PET patterns in patients with corticobasal syndrome are characterized by asymmetrical uptake in the motor cortex and underlying white matter, as well as in the basal ganglia. Even in the patients with multiple system atrophy, which is basically a synucleinopathy, ¹⁸F-flortaucipir, a widely used tau PET tracer, also binds to the atrophic posterior putamen, possibly due to off-target binding. These distinct patterns of tau-selective radiotracer binding in the various degenerative parkinsonisms suggest its utility as a potential imaging biomarker for the differential diagnosis of parkinsonisms.


Assuntos
Doença de Alzheimer , Gânglios da Base , Diagnóstico Diferencial , Elétrons , Globo Pálido , Humanos , Corpos de Lewy , Mesencéfalo , Córtex Motor , Atrofia de Múltiplos Sistemas , Emaranhados Neurofibrilares , Transtornos Parkinsonianos , Patologia , Tomografia por Emissão de Pósitrons , Putamen , Paralisia Supranuclear Progressiva , Proteínas tau , Substância Branca
8.
Dement. neuropsychol ; 11(2): 198-201, Apr.-June 2017.
Artigo em Inglês | LILACS (Américas) | ID: biblio-890997

RESUMO

ABSTRACT Fritz Jacob Heinrich Lewy described the pathology of Paralysis agitans [Parkinson disease] and was the first to identify eosinophilic inclusion bodies in neurons of certain brain nuclei, later known as Lewy bodies, the pathological signature of the Lewy body diseases. In 1912, he published his seminal study, followed soon after by an update paper, and 10 years later, in 1923, by his voluminous book, where he exhaustively described the subject. The publication provided extensive information on the pathology of Paralysis agitans, and the entirely novel finding of eosinophilic inclusion bodies, which would become widely recognized and debated in the future. His discovery was acknowledged by important researchers who even named the structure after him. However, after his last publication on the issue, inexplicably, he never mentioned his histopathological discovery again. Despite several hypotheses, the reasons that led him to neglect (reject) the structure which he so preeminently described have remained elusive.


RESUMO Fritz Jacob Heinrich Lewy descreveu a patologia da Paralysis agitans [doença de Parkinson] e identificou pela primeira vez corpos de inclusão eosinófílos em neurônios de certos núcleos cerebrais, conhecidos mais tarde como corpos de Lewy, assinatura patológica das doenças dos corpos de Lewy. Ele divulgou em 1912 seu trabalho seminal, seguido logo por um artigo de atualização e 10 anos depois, em 1923, seu volumoso livro onde detalhou exaustivamente o assunto. Ali ele trouxe extensa informação sobre a patologia da Paralysis agitans e um achado inteiramente novo, os corpos de inclusão eosinófilos, que seriam valorizados e largamente debatidos no futuro. Seu achado foi reconhecido por importantes pesquisadores que até designaram essa estrutura com seu nome. Entretanto, após sua última publicação sobre o assunto, inexplicavelmente , ele nunca mais mencionou sua descoberta histopatológica. Apesar de diversas hipóteses, a razão que o levou negligenciar (rejeitar) a estrutura, que teve a primazia de descrever, permaneceu desconhecida.


Assuntos
Humanos , Doença de Parkinson , Corpos de Inclusão , Corpos de Lewy , Eosinófilos
9.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-152983

RESUMO

OBJECTIVE: Donepezil is used to improve cognitive impairment of dementia with Lewy bodies (DLB). Visuo-spatial dysfunction is a well-known symptom of DLB. Non-verbal Raven’s Colored Progressive Matrices (RCPM) were used to assess both visual perception and reasoning ability in DLB subjects treated with donepezil. METHODS: Twenty-one DLB patients (mean age, 78.7±4.5 years) were enrolled. RCPM assessment was performed at the time of starting donepezil and within one year after starting donepezil. RESULTS: There were significant improvements of RCPM in the total scores between one year donepezil treatment (p=0.013), in both Set A score (p=0.002) and Set AB score (p=0.015), but trend in the Set B score (p=0.083). CONCLUSION: Donepezil is useful for improving visuo-spatial impairment in DLB, but not for problem-solving impairment.


Assuntos
Inibidores da Colinesterase , Transtornos Cognitivos , Demência , Humanos , Corpos de Lewy , Doença por Corpos de Lewy , Processamento Espacial , Percepção Visual
10.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-38089

RESUMO

Parkinson's disease (PD), the second most common neurodegenerative disorder after Alzheimer's disease, is characterized by the loss of nigral dopaminergic neurons. PD leads to a series of clinical symptoms, including motor and non-motor disturbances. α-synuclein, the major component of Lewy bodies, is a hallmark lesion in PD. In this review, we concentrate on presenting the latest research on the structure, distribution, and function of α-synuclein, and its interactions with PD. We also summarize the clinic applications of α-synuclein, which suggest its use as a biomarker, and the latest progress in α-synuclein therapy.


Assuntos
alfa-Sinucleína , Doença de Alzheimer , Neurônios Dopaminérgicos , Corpos de Lewy , Doenças Neurodegenerativas , Doença de Parkinson
11.
Chonnam Medical Journal ; : 145-150, 2016.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-788354

RESUMO

¹²³I-meta-iodobenzylguanidine (MIBG) has become widely applied in Japan since its introduction to clinical cardiology and neurology practice in the 1990s. Neurological studies found decreased cardiac uptake of ¹²³I-MIBG in Lewy-body diseases including Parkinson's disease and dementia with Lewy bodies. Thus, cardiac MIBG uptake is now considered a biomarker of Lewy body diseases. Although scintigraphic images of ¹²³I-MIBG can be visually interpreted, an average count ratio of heart-to-mediastinum (H/M) has commonly served as a semi-quantitative marker of sympathetic activity. Since H/M ratios significantly vary according to acquisition and processing conditions, quality control should be appropriate, and quantitation should be standardized. The threshold H/M ratio for differentiating Lewy-body disease is 2.0-2.1, and was based on standardized H/M ratios to comparable values of medium-energy collimators. Parkinson's disease can be separated from various types of parkinsonian syndromes using cardiac ¹²³I-MIBG, whereas activity is decreased on images of Lewy-body diseases using both ¹²³I-ioflupane for the striatum and ¹²³I-MIBG. Despite being a simple index, the H/M ratio of ¹²³I-MIBG uptake is reproducible and can serve as an effective tool to support a diagnosis of Lewy-body diseases in neurological practice.


Assuntos
3-Iodobenzilguanidina , Cardiologia , Demência , Diagnóstico , Japão , Corpos de Lewy , Doença por Corpos de Lewy , Neurologia , Medicina Nuclear , Doença de Parkinson , Transtornos Parkinsonianos , Controle de Qualidade
12.
Artigo em Coreano | WPRIM (Pacífico Ocidental) | ID: wprim-725340

RESUMO

Dementia with Lewy bodies (DLB) is the second most common causes of dementia. It can exhibit a variety of clinical symptoms including cognitive decline, cognitive fluctuation, visual hallucinations, parkinsonism, REM sleep behavior disorder, hypersensitivity to neuroleptics and autonomic dysfunctions. Despite more well-known criteria for DLB, there are often misdiagnosis and inappropriate treatment. It gives a lot of clinical burden to the clinician as well as to patients and families. When reducing the misdiagnosis, the burden of all will be reduced. The special concern and solicitation are needed in order not to miss the diagnosis when the cardinal features of DLB may not be volunteered by patients and the caregivers. To control the symptoms, clinicians must find and reduce drugs that can have the negative effects on DLB symptoms. There is limited evidence about specific interventions but available data suggest cholinesterase inhibitors improve the cognitive and behavioral symptoms and menmantine slightly improves the global impression.


Assuntos
Antipsicóticos , Sintomas Comportamentais , Cuidadores , Inibidores da Colinesterase , Demência , Diagnóstico , Erros de Diagnóstico , Alucinações , Humanos , Hipersensibilidade , Corpos de Lewy , Transtornos Parkinsonianos , Transtorno do Comportamento do Sono REM
13.
Experimental Neurobiology ; : 113-119, 2016.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-213646

RESUMO

Synucleinopathies are a collection of neurological diseases that are characterized by deposition of α-synuclein aggregates in neurons and glia. These diseases include Parkinson's disease (PD), dementia with Lewy bodies, and multiple system atrophy. Although it has been increasingly clear that α-synuclein is implicated in the pathogenesis of PD and other synucleinopathies, the precise mechanism underlying the disease process remains to be unraveled. The past studies on how α-synuclein exerts pathogenic actions have focused on its direct, cell-autonomous neurotoxic effects. However, recent findings suggested that there might be indirect, non-cell-autonomous pathways, perhaps through the changes in glial cells, for the pathogenic actions of this protein. Here, we present evidence that α-synuclein can cause neurodegeneration through a non-cell-autonomous manner. We show that α-synuclein can be secreted from neurons and induces inflammatory responses in microglia, which in turn secreted neurotoxic agents into the media causing neurodegeneration. The neurotoxic response of microglia was mediated by activation of toll-like receptor 2 (TLR2), a receptor for neuron-derived α-synuclein. This work suggests that TLR2 is the key molecule that mediates non-cell-autonomous neurotoxic effects of α-synuclein, hence a candidate for the therapeutic target.


Assuntos
Demência , Corpos de Lewy , Microglia , Atrofia de Múltiplos Sistemas , Neuroglia , Neurônios , Doença de Parkinson , Receptor 2 Toll-Like , Receptores Toll-Like
14.
Chonnam Medical Journal ; : 145-150, 2016.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-25334

RESUMO

¹²³I-meta-iodobenzylguanidine (MIBG) has become widely applied in Japan since its introduction to clinical cardiology and neurology practice in the 1990s. Neurological studies found decreased cardiac uptake of ¹²³I-MIBG in Lewy-body diseases including Parkinson's disease and dementia with Lewy bodies. Thus, cardiac MIBG uptake is now considered a biomarker of Lewy body diseases. Although scintigraphic images of ¹²³I-MIBG can be visually interpreted, an average count ratio of heart-to-mediastinum (H/M) has commonly served as a semi-quantitative marker of sympathetic activity. Since H/M ratios significantly vary according to acquisition and processing conditions, quality control should be appropriate, and quantitation should be standardized. The threshold H/M ratio for differentiating Lewy-body disease is 2.0-2.1, and was based on standardized H/M ratios to comparable values of medium-energy collimators. Parkinson's disease can be separated from various types of parkinsonian syndromes using cardiac ¹²³I-MIBG, whereas activity is decreased on images of Lewy-body diseases using both ¹²³I-ioflupane for the striatum and ¹²³I-MIBG. Despite being a simple index, the H/M ratio of ¹²³I-MIBG uptake is reproducible and can serve as an effective tool to support a diagnosis of Lewy-body diseases in neurological practice.


Assuntos
3-Iodobenzilguanidina , Cardiologia , Demência , Diagnóstico , Japão , Corpos de Lewy , Doença por Corpos de Lewy , Neurologia , Medicina Nuclear , Doença de Parkinson , Transtornos Parkinsonianos , Controle de Qualidade
15.
Rev. Kairós ; 18(4): 398-404, dez. 2015.
Artigo em Português | LILACS (Américas) | ID: biblio-986243

RESUMO

O presente trabalho é uma revisão bibliográfica com o objetivo de identificar e apresentar as produções científicas relacionadas à atuação da fisioterapia especificamente na Demência por Corpúsculos de Lewy (DCL). O critério de exclusão da pesquisa são estudos que tratam da atuação da fisioterapia na Doença de Alzheimer (DA) e na Doença de Parkinson (DP, que precede a síndrome demencial). Conclui-se que não existem estudos com resultados conclusivos sobre a atuação da fisioterapia na DCL


This study is a literature review in order to identify and present the scientific production related to the role of physiotherapy specifically in dementia by Lewy bodies. The search criterion for exclusion are the physiotherapy performance of studies in Alzheimer's disease and Parkinson's disease (which precedes dementia). It is concluded that there are insufficient studies for a possible review and discussion of the role of physiotherapy.


Assuntos
Humanos , Reabilitação , Bases de Dados Bibliográficas , Corpos de Lewy , Fisioterapia , Demência , Doença Crônica
16.
Artigo em Coreano | WPRIM (Pacífico Ocidental) | ID: wprim-203518

RESUMO

Pharmacological interventions are critical in dementia treatment to prevent disease progression. In this review, we aim to summarize and discuss about the current developments and recommendations in the pharmacological treatment of dementia. Cholinesterase inhibitors have demonstrated efficacy for Alzheimer's disease, mixed pathology with vascular dementia and Parkinson's disease dementia. The comparison study revealed no difference between each cholinesterase inhibitors. A high incidence of side effects of cholinesterase inhibitors could lower compliance. In this case, changing to the other drug or trying a transdermal type could be the solution. Memantine, a N-methyl-D-aspartate receptor antagonist, has proven to improve function at moderate to severe dementia and for dementia with Lewy body. But there are still insufficient evidences for the combination of a cholinesterase inhibitors and memantine. Discontinuing medicine in moderate to severe dementia may lead to worsening of cognitive function. For this reason, improving patients' compliance is important and for drug selection we should consider the type of dementia, severity of cognitive impairment and side effects of each medicine. Noncognitive symptoms, behavioral and psychological symptoms of dementia (BPSD) are common and can dominate disease presentation. For depression, selective serotonin reuptake inhibitors could be effective. Atypical antipsychotics could be used for other neuropsychological symptoms such as agitation, aggression, delusions and hallucinations.


Assuntos
Agressão , Doença de Alzheimer , Antipsicóticos , Sintomas Comportamentais , Inibidores da Colinesterase , Complacência (Medida de Distensibilidade) , Delusões , Demência , Demência Vascular , Depressão , Di-Hidroergotamina , Progressão da Doença , Alucinações , Incidência , Corpos de Lewy , Memantina , N-Metilaspartato , Doença de Parkinson , Patologia , Inibidores de Captação de Serotonina
17.
Experimental Neurobiology ; : 292-313, 2014.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-113795

RESUMO

Alpha-synuclein is a small neuronal protein that is closely associated with the etiology of Parkinson's disease. Mutations in and alterations in expression levels of alpha-synuclein cause autosomal dominant early onset heredity forms of Parkinson's disease, and sporadic Parkinson's disease is defined in part by the presence of Lewy bodies and Lewy neurites that are composed primarily of alpha-synuclein deposited in an aggregated amyloid fibril state. The normal function of alpha-synuclein is poorly understood, and the precise mechanisms by which it leads to toxicity and cell death are also unclear. Although alpha-synuclein is a highly soluble, cytoplasmic protein, it binds to a variety of cellular membranes of different properties and compositions. These interactions are considered critical for at least some normal functions of alpha-synuclein, and may well play critical roles in both the aggregation of the protein and its mechanisms of toxicity. Here we review the known features of alpha-synuclein membrane interactions in the context of both the putative functions of the protein and of its pathological roles in disease.


Assuntos
alfa-Sinucleína , Amiloide , Morte Celular , Citoplasma , Hereditariedade , Corpos de Lewy , Membranas , Neuritos , Neurônios , Doença de Parkinson , Transmissão Sináptica
18.
Experimental Neurobiology ; : 337-344, 2014.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-113792

RESUMO

Multiple system atrophy (MSA) is a rare, yet fatal neurodegenerative disease that presents clinically with autonomic failure in combination with parkinsonism or cerebellar ataxia. MSA impacts on the autonomic nervous system affecting blood pressure, heart rate and bladder function, and the motor system affecting balance and muscle movement. The cause of MSA is unknown, no definitive risk factors have been identified, and there is no cure or effective treatment. The definitive pathology of MSA is the presence of alpha-synuclein aggregates in the brain and therefore MSA is classified as an alpha-synucleinopathy, together with Parkinson's disease and dementia with Lewy bodies. Although the molecular mechanisms of misfolding, fibrillation and aggregation of alpha-synuclein partly overlap with other alpha-synucleinopathies, the pathological pathway of MSA is unique in that the principal site for alpha-synuclein deposition is in the oligodendrocytes rather than the neurons. The sequence of pathological events of MSA is now recognized as abnormal protein redistributions in oligodendrocytes first, followed by myelin dysfunction and then neurodegeneration. Oligodendrocytes are responsible for the production and maintenance of myelin, the specialized lipid membrane that encases the axons of all neurons in the brain. Myelin is composed of lipids and two prominent proteins, myelin basic protein and proteolipid protein. In vitro studies suggest that aberration in protein distribution and lipid transport may lead to myelin dysfunction in MSA. The purpose of this perspective is to bring together available evidence to explore the potential role of alpha-synuclein, myelin protein dysfunction, lipid dyshomeostasis and ABCA8 in MSA pathogenesis.


Assuntos
alfa-Sinucleína , Sistema Nervoso Autônomo , Axônios , Pressão Sanguínea , Encéfalo , Ataxia Cerebelar , Demência , Frequência Cardíaca , Corpos de Lewy , Membranas , Atrofia de Múltiplos Sistemas , Proteínas da Mielina , Bainha de Mielina , Doenças Neurodegenerativas , Neurônios , Oligodendroglia , Doença de Parkinson , Transtornos Parkinsonianos , Patologia , Fatores de Risco , Bexiga Urinária
19.
Experimental Neurobiology ; : 352-364, 2014.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-113790

RESUMO

The clinical diagnostic criteria of Parkinson's disease (PD) have limitations in detecting the disease at early stage and in differentiating heterogeneous clinical progression. The lack of reliable biomarker(s) for early diagnosis and prediction of prognosis is a major hurdle to achieve optimal clinical care of patients and efficient design of clinical trials for disease-modifying therapeutics. Numerous efforts to discover PD biomarkers in CSF were conducted. In this review, we describe the molecular pathogenesis of PD and discuss its implication to develop PD biomarkers in CSF. Next, we summarize the clinical utility of CSF biomarkers including alpha-synuclein for early and differential diagnosis, and prediction of PD progression. Given the heterogeneity in the clinical features of PD and none of the CSF biomarkers for an early diagnosis have been developed, research efforts to develop biomarkers to predict heterogeneous disease progression is on-going. Notably, a rapid cognitive decline followed by the development of dementia is a risk factor of poor prognosis in PD. In connection to this, CSF levels of Alzheimer's disease (AD) biomarkers have received considerable attention. However, we still need long-term longitudinal observational studies employing large cohorts to evaluate the clinical utility of CSF biomarkers reflecting Lewy body pathology and AD pathology in the brain. We believe that current research efforts including the Parkinson's Progression Markers Initiative will resolve the current needs of early diagnosis and/or prediction of disease progression using CSF biomarkers, and which will further accelerate the development of disease-modifying therapeutics and optimize the clinical management of PD patients.


Assuntos
alfa-Sinucleína , Doença de Alzheimer , Biomarcadores , Encéfalo , Líquido Cefalorraquidiano , Estudos de Coortes , Demência , Diagnóstico Diferencial , Progressão da Doença , Diagnóstico Precoce , Humanos , Corpos de Lewy , Doença de Parkinson , Patologia , Características da População , Prognóstico , Fatores de Risco
20.
Hanyang Medical Reviews ; : 116-119, 2014.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-103510

RESUMO

Olfactory dysfunction is an early and common symptom of many neurodegenerative diseases, particularly of Parkinson's disease, Alzheimer's disease, and mild cognitive impairment that heralds progression to dementia. Olfactory impairment is known to be related to several pathologic changes including the deposition of alpha-synuclein, hyperphosphorylated tau protein, neurofilament protein, Lewy bodies and neuritis inducing a complex cascade of molecular processes such as oxidative stress, neuroinflammation, and cytosolic disruption of cellular processes leading to cell death. The areas mainly showing these pathologic changes are the olfactory epithelium, olfactory bulb and tract, primary olfactory cortices, and their secondary target areas. Since early loss of olfactory function is common among several common neurodegenerative disorders, recent investigations have focused on its utility as a biomarker for early diagnosis and progression. Olfactory impairment appears to be an important sign for early detection, a useful biomarker for disease progression and a useful differentiator between neurological disorders.


Assuntos
alfa-Sinucleína , Doença de Alzheimer , Morte Celular , Citosol , Demência , Progressão da Doença , Diagnóstico Precoce , Corpos de Lewy , Disfunção Cognitiva , Doenças do Sistema Nervoso , Neurite (Inflamação) , Doenças Neurodegenerativas , Bulbo Olfatório , Mucosa Olfatória , Estresse Oxidativo , Doença de Parkinson , Olfato , Proteínas tau , Biomarcadores
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