Abnormal distribution of cathepsins in the brain of patients with Alzheimer's disease

Nakamura, Yu; Takeda, Masatoshi; Suzuki, Hideo; Hattori, Hideyuki; Tada, Kazuya; Hariguchi, Shiro; Hashimoto, Shigeo; Nishimura, Tsuyoshi

doi:10.1016/0304-3940(91)90395-a

Cited by 106 publications

(36 citation statements)

References 9 publications

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“…Consistent with this idea is the previously reported finding that another lysosomal hydrolase, cathepsin S, exhibits increased expression in the scrapie-infected mouse brain (7). The altered production and distribution of lysosomal hydrolases have also been reported in other neurodegenerative disorders (5,19,21). The physiological function of lysozyme M is unclear, but it is known to degrade peptidoglycan components of the bacterial cell wall, and it is a useful marker for mature and activated macrophages (17).…”

Section: Discussionmentioning

confidence: 91%

Upregulation of the Genes Encoding Lysosomal Hydrolases, a Perforin-Like Protein, and Peroxidases in the Brains of Mice Affected with an Experimental Prion Disease

Kopáček

Sakaguchi²,

Shigematsu³

et al. 2000

J Virol

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In an attempt to identify the molecules involved in the pathogenesis of prion diseases, we performed cDNA subtraction on the brain tissues of mice affected with an experimental prion disease and the unaffected control. The genes identified as being upregulated in the prion-affected brain tissue included those encoding a series of lysosomal hydrolases (lysozyme M and both isoforms of ␤-N-acetylhexosaminidase), a perforin-like protein (macrophage proliferation-specific gene-1 [MPS-1]), and an oxygen radical scavenger (peroxiredoxin). Dramatic increases in the expression level occurred at between 12 and 16 weeks after intracerebral inoculation of the prion, coinciding with the onset of spongiform degeneration. The proteinase K-resistant prion protein (PrP Sc ) became detectable by immunoblotting well before 12 weeks, suggesting a causal relationship between this and the gene activation. Immunohistochemistry paired with in situ hybridization on sections of the affected brain tissue revealed that expression of the peroxiredoxin gene was detectable only in astrocytes and was noted throughout the affected brain tissue. On the other hand, the genes for the lysosomal hydrolases and MPS-1 were overexpressed exclusively by microglia, which colocalized with the spongiform morphological changes. A crucial role for microglia in the spongiform degeneration by their production of neurotoxic substances, and possibly via the aberrant activation of the lysosomal system, would have to be considered.

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Section: Discussionmentioning

confidence: 91%

Upregulation of the Genes Encoding Lysosomal Hydrolases, a Perforin-Like Protein, and Peroxidases in the Brains of Mice Affected with an Experimental Prion Disease

Kopáček

Sakaguchi²,

Shigematsu³

et al. 2000

J Virol

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“…Polyclonal sheep anti-human CB antiserum was purchased from The Binding Site Ltd (Birmingham, England), and the specificity of the antiserum was confirmed by Western blotting and immunodiffusion experiment as previously described (Burnett and Stockley 1985;Nakamura et al 1991). The monoclonal rabbit anti-human type IV collagen (CIV) antibody and the polyclonal rabbit anti-mouse laminin (LM) antibody were purchased from Advance Ltd (Tokyo, Japan) and E-Y Laboratories Inc. (San Mateo, Calif., USA), respectively.…”

Section: Methodsmentioning

confidence: 99%

Immunohistochemical distributions of cathepsin B and basement membrane antigens in human lung adenocarcinoma: association with invasion and metastasis

Sukoh

Abe

Nakajima

et al. 1994

Vichows Archiv A Pathol Anat

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The distributions of cathepsin B (CB) a lysosomal cysteine proteinase, type IV collagen (CIV) and laminin (LM), which are main components of basement membranes (BMs) were studied in a series of 64 human lung adenocarcinomas using an immunohistochemical technique. Over-expression of CB (> 80% positive cells) was significantly associated with the grade of tumour differentiation (p < 0.01), with lymph node metastasis (p < 0.01) and with BM degradation (p < 0.01) detected by the staining pattern of CIV and LM. It was significantly associated with a prognostic disadvantage (p < 0.01). The immunohistochemical staining pattern of CB has a close relationship with degradation of BM, and may be used as a marker for tumour metastasis and prognosis in lung adenocarcinoma.

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“…The astrocytic compartment may also contribute substantially to the pathogenesis of Alzheimer's disease by serving as an important site for cathepsin mediated proteolysis, amyloid metabolism, cytoskeletal protein hyperphosphorylation and the expression of apolipoprotein E (Oropeza, R. et al 1987;Nakamura et al, 1991;Eddelston,M., et al, 1993;Nieto-Sampedro and Mora, 1994). As described in the following actions, the unique histochemical properties of Gomori-positive astrocytes suggest that those celis may play an important role in brain aging and neurodegeneration.…”

Section: • Palhological Effecls Of Aslrocyles In Lhe Cnsmentioning

confidence: 99%

Differential effects of cysteamine on heat shock protein induction and cytoplasmic granulation in astrocytes and glioma cells

Chopra¹,

Chalifour²,

Schipper³

1995

Molecular Brain Research

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Abnormal distribution of cathepsins in the brain of patients with Alzheimer's disease

Cited by 106 publications

References 9 publications

Upregulation of the Genes Encoding Lysosomal Hydrolases, a Perforin-Like Protein, and Peroxidases in the Brains of Mice Affected with an Experimental Prion Disease

Upregulation of the Genes Encoding Lysosomal Hydrolases, a Perforin-Like Protein, and Peroxidases in the Brains of Mice Affected with an Experimental Prion Disease

Immunohistochemical distributions of cathepsin B and basement membrane antigens in human lung adenocarcinoma: association with invasion and metastasis

Differential effects of cysteamine on heat shock protein induction and cytoplasmic granulation in astrocytes and glioma cells

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