Localization of HtrA2/Omi immunoreactivity in brains affected by Alzheimer’s disease

Kawamoto, Yuko; Ito, Hidefumi; Kobayashi, Yasue; Suzuki, Yasuyuki; Takahashi, Ryōsuke

doi:10.1097/wnr.0b013e328340a731

Cited by 6 publications

(5 citation statements)

References 20 publications

(25 reference statements)

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“…4b). These immunostaining patterns were similar to those of HtrA2/Omi in brains with Alzheimer's disease [12], and our results indicate that neither XIAP nor HtrA2/Omi accumulate specifically in brainstem-type and cortical Lewy bodies.…”

Section: X-linked Inhibitor Of Apoptosis Protein Immunoreactivity In supporting

confidence: 78%

Immunohistochemical localization of X-linked inhibitor of apoptosis protein in brainstem-type and cortical Lewy bodies

Kawamoto

Ito²,

Ihara³

et al. 2012

NeuroReport

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X-linked inhibitor of apoptosis protein (XIAP) blocks the apoptosis by binding to and inhibiting caspases-3, 7, and 9. XIAP is negatively regulated by the mitochondrial serine protease, HtrA2/Omi. The aim of this study was to investigate the role of XIAP and the relationship between XIAP and HtrA2/Omi in patients with Parkinson's disease or dementia with Lewy bodies. We conducted immunohistochemical studies on XIAP in formalin-fixed, paraffin-embedded sections from eight normal participants, 10 patients with Parkinson's disease, five patients with dementia with Lewy bodies, and seven patients with Alzheimer's disease, and then double-labeling immunohistochemistry for XIAP and HtrA2/Omi in sections from the Parkinson's disease and dementia with Lewy bodies cases. Brainstem-type and cortical Lewy bodies were intensely immunostained for XIAP, and XIAP immunoreactivity was localized to the halos of brainstem-type Lewy bodies and to the entire bodies of cortical Lewy bodies. Double immunofluorescence analyses showed that XIAP and HtrA2/Omi immunoreactivities were colocalized to both types of Lewy bodies. Our results suggest that XIAP may be partially associated with the pathogenesis of Parkinson's disease and dementia with Lewy bodies.

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Section: X-linked Inhibitor Of Apoptosis Protein Immunoreactivity In supporting

confidence: 78%

Immunohistochemical localization of X-linked inhibitor of apoptosis protein in brainstem-type and cortical Lewy bodies

Kawamoto

Ito²,

Ihara³

et al. 2012

NeuroReport

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“…A later study demonstrated that HtrA2/Omi performs a chaperone function and significantly delays the aggregation of Aβ 1-42 peptide but independent of the PDZ domain in vitro [247]. Densely accumulated HtrA2 immunoreactivity was identified extracellularly in the cortex and hippocampus of AD patients [248], suggesting changes in HtrA2 may affect amyloid deposition extracellularly which is consistent with the partial localization of HtrA2 immunoreactivity in amyloid plaques. However, the physiological significance of these observations in vivo as it relates to mitochondria is unclear.…”

Section: Impaired Mitochondrial Proteostasis In Admentioning

confidence: 58%

Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: recent advances

Wang

Zhao

et al. 2020

Mol Neurodegeneration

699

506

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Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases, characterized by impaired cognitive function due to progressive loss of neurons in the brain. Under the microscope, neuronal accumulation of abnormal tau proteins and amyloid plaques are two pathological hallmarks in affected brain regions. Although the detailed mechanism of the pathogenesis of AD is still elusive, a large body of evidence suggests that damaged mitochondria likely play fundamental roles in the pathogenesis of AD. It is believed that a healthy pool of mitochondria not only supports neuronal activity by providing enough energy supply and other related mitochondrial functions to neurons, but also guards neurons by minimizing mitochondrial related oxidative damage. In this regard, exploration of the multitude of mitochondrial mechanisms altered in the pathogenesis of AD constitutes novel promising therapeutic targets for the disease. In this review, we will summarize recent progress that underscores the essential role of mitochondria dysfunction in the pathogenesis of AD and discuss mechanisms underlying mitochondrial dysfunction with a focus on the loss of mitochondrial structural and functional integrity in AD including mitochondrial biogenesis and dynamics, axonal transport, ER-mitochondria interaction, mitophagy and mitochondrial proteostasis.

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“…Until now, only one study has analyzed OMI/HTRA2 in human brain material, although biochemical studies using cell culture conditions or isolated proteins have reported an interaction of OMI/HTRA2 with key factors of the AD pathology: A β (4, 28), APP (6), PS1 (1), and 7 ‐secretase (3). Recently, Kawamoto et al (22) reported for the first time abnormal accumulation of OMI/HTRA2 immu‐noreactivity in senile plaques and neurofibrillary tangles, the neuropathological hallmarks of AD, but the researchers caution that the finding might be nonspecific and that further analyses of human brain tissue are necessary to clarify the role of OMI/HTRA2 in AD.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the biochemical studies implicating OMI/HTRA2 in AD pathology, few data are available on possible changes in expression levels or enzyme activity in AD brain tissue. A recent report showed that in AD brain tissue, OMI/HTRA2 immunoreactivity localizes to senile plaques and neurofibrillary tangles (22). We investigated proteolytic activity and expression of OMI/HTRA2 in human postmortem brain tissues and analyzed the occurrence of the protease‐deficient gene variants A141S and G399S in Swedish AD and PD case‐control samples.…”

mentioning

confidence: 99%

Altered enzymatic activity and allele frequency of OMI/HTRA2 in Alzheimer's disease

Westerlund¹,

Behbahani

Gellhaar³

et al. 2010

FASEB j.

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The serine-protease OMI/HTRA2, required for several cellular processes, including mitochondrial function, autophagy, chaperone activity, and apoptosis, has been implicated in the pathogenesis of both Alzheimer's disease (AD) and Parkinson's disease (PD). Western blot quantification of OMI/HTRA2 in frontal cortex of patients with AD (n=10) and control subjects (n=10) in two separate materials indicated reduced processed (active, 35 kDa) OMI/HTRA2 levels, whereas unprocessed (50 kDa) enzyme levels were not significantly different between the groups. Interestingly, the specific protease activity of OMI/HTRA2 was found to be significantly increased in patients with AD (n=10) compared to matched control subjects (n=10) in frontal cortex in two separate materials. Comparison of OMI/HTRA2 mRNA levels in frontal cortex and hippocampus, two brain areas particularly affected by AD, indicated similar levels in patients with AD (n=10) and matched control subjects (n=10). In addition, we analyzed the occurrence of the OMI/HTRA2 variants A141S and G399S in Swedish case-control materials for AD and PD and found a weak association of A141S with AD, but not with PD. In conclusion, our genetic, histological, and biochemical findings give further support to an involvement of OMI/HTRA2 in the pathology of AD; however, further studies are needed to clarify the role of this gene in neurodegeneration.

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Localization of HtrA2/Omi immunoreactivity in brains affected by Alzheimer’s disease

Cited by 6 publications

References 20 publications

Immunohistochemical localization of X-linked inhibitor of apoptosis protein in brainstem-type and cortical Lewy bodies

Immunohistochemical localization of X-linked inhibitor of apoptosis protein in brainstem-type and cortical Lewy bodies

Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: recent advances

Altered enzymatic activity and allele frequency of OMI/HTRA2 in Alzheimer's disease

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