Body-like Inclusions (body-like + inclusion)

Distribution by Scientific Domains
Medical Sciences50%
Life Sciences50%

Kinds of Body-like Inclusions

  • lewy body-like inclusion
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    Selected Abstracts

    Oxidative modification of mitochondrial proteins and cell death in Parkinson's disease

    JOURNAL OF NEUROCHEMISTRY, Issue 2002
    W. Maruyama
    Oxidative stress is one of the cell death mechanisms in neurodegenerative disorders, such as Parkinson's disease (PD) and Alzheimer's disease. Most of reactive oxygen species (ROS) generate in mitochondria through oxidative phosphorylation, and a part of them are not scavenged by antioxidative system and react with bioactive molecules. Recently, alpha-synuclein containing nitrotyrosine, a marker for oxidative modification by peroxynitrite, was identified in Lewy body. In addition, inhibitors of mitochondrial respiratory chain were reported to induce formation of Lewy body-like inclusion in vivo and in vitro. In this paper it was examined whether ROS and reactive nitrogen species (RNS) generated in mitochondria oxidize mitochondrial respiratory enzymes and induce the formation of inclusion body and cell death in PD. Human neuroblastoma SH-SY5Y cells were treated with a peroxynitrite donor, SIN-1, or an inhibitor of complex I, rotenone. After the treatment, proteins modified with toxic aldehydes, 4-hydroxynonenal and acrolein, and containing nitrotyrosine were analyzed by immunoblotting. Particularly in mitochondrial fraction, the oxidized protein was characterized by two-dimensional immunoblotting. Most of the oxidized proteins were detected in subunits proteins of complex I. These results indicate that mitochondrial complex I is a main target of oxidative stress in dopamine neurons and its dysfunction may be involved in the death mechanism in neurodegenerative disorders. [source]

    Pro-apoptotic protein glyceraldehyde-3-phosphate dehydrogenase promotes the formation of Lewy body-like inclusions

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2005
    Katsumi Tsuchiya
    Abstract Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has long been recognized as a classical glycolytic protein; however, previous studies by our group and others have demonstrated that GAPDH is a general mediator initiating one or more apoptotic cascades. Our most recent findings have elucidated that an expression of a pro-apoptotic protein GAPDH is critically regulated at the promoter region of the gene. Apoptotic signals for its subsequent aggregate formation and nuclear translocation are controlled by the respective functional domains harboured within its cDNA component. In this study, coexpression of GAPDH with either wild-type or mutant (A53T) ,-synuclein and less likely with ,-synuclein in transfected COS-7 cells was found to induce Lewy body-like cytoplasmic inclusions. Unlike its full-length construct, the deleted mutant GAPDH construct (C66) abolished these apoptotic signals, disfavouring the formation of inclusions. The generated inclusions were ubiquitin- and thioflavin S-positive appearing fibrils. Furthermore, GAPDH coimmunoprecipitated with wild-type ,-synuclein in this paradigm. Importantly, immunohistochemical examinations of post mortem materials from patients with sporadic Parkinson's disease revealed the colocalized profiles immunoreactive against these two proteins in the peripheral zone of Lewy bodies from the affected brain regions (i.e. locus coeruleus). Moreover, a quantitative assessment showed that about 20% of Lewy bodies displayed both antigenicities. These results suggest that pro-apoptotic protein GAPDH may be involved in the Lewy body formation in vivo, probably associated with the apoptotic death pathway. [source]

    Changes in age-associated neurodegenerative diseases in the last half century

    GERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 3 2002
    Asao Hirano
    Age-associated neurodegenerative diseases are a serious and growing problem for mankind, and their etiologies are still unknown. The author has been studying the neuropathology of fatal neurodegenerative diseases endemic to the native Chamorro population on Guam during the last half a century. During this time, remarkable advances in scientific technology, such as the application of electron microscopy, immunohistochemistry and molecular genetics, have contributed to numerous discoveries in classic neurological diseases. In addition, various new diseases have been recognized. This communication reviews Alzheimer's neurofibrillary tangles and Cu/Zn superoxide dismutase positive Lewy body-like inclusions in the anterior horn cells, in order to elucidate these pathological findings as well as remarkable changes observed in certain other age-related neurodegenerative diseases. [source]

    Involvement of spinal motor neurons in parkin-positive autosomal recessive juvenile parkinsonism

    NEUROPATHOLOGY, Issue 1 2008
    Shoichi Sasaki
    We intensively examined the spinal cord of an autosomal recessive juvenile parkinsonism (ARJP) female patient with a homozygous exon 3 deletion in the parkin gene, anticipating a possible involvement of anterior horn neurons. Although the clinical features of the patient were consistent with parkinsonism as a result of parkin mutation, her tendon reflex was abolished in the lower limbs. This feature was in contrast with hyperreflexia, usually found in previous reports of ARJP. Histologically, on the level of the cervical, thoracic, and sacral spinal cord, anterior horn neurons were well preserved and normal. However, the lumbar spinal cord exhibited many swellings of proximal axons (spheroids) and degenerative changes in the somata of the large anterior horn neurons such as central chromatolysis, cystatin C-negative small eosinophilic inclusions, and eosinophilic Lewy body-like inclusions. Ultrastructurally, accumulations of neurofilaments and abnormal structures, such as inclusion bodies similar to skein-like inclusions and disorganized rough endoplasmic reticulum, were observed in the somata and neuronal processes. Lewy body-like inclusions in this study were positively immunostained for both ,-synuclein and ubiquitin that closely resemble Lewy bodies, but are different from Lewy body-like inclusions negatively immunostained for ,-synuclein in amyotrophic lateral sclerosis. These findings suggest that eosinophilic inclusions that closely resemble Lewy bodies may be formed in the spinal motor neurons of ARJP patients with parkin mutations and the motor neurons of these patients may be vulnerable to neurodegeneration. [source]