Abstract:
:beta-Secretase, a beta-site amyloid precursor protein (APP) cleaving enzyme (BACE), participates in the secretion of beta-amyloid peptides (Abeta), the major components of the toxic amyloid plaques found in the brains of patients with Alzheimer's disease (AD). According to the amyloid hypothesis, accumulation of Abeta is the primary influence driving AD pathogenesis. Lowering of Abeta secretion can be achieved by decreasing BACE activity rather than by down-regulation of the APP substrate protein. Therefore, beta-secretase is a primary target for anti-amyloid therapeutic drug design. Several approaches have been undertaken to find an effective inhibitor of human beta-secretase activity, mostly in the field of peptidomimetic, non-cleavable substrate analogues. This review describes strategies targeting BACE mRNA recognition and its down-regulation based on the antisense action of small inhibitory nucleic acids (siNAs). These include antisense oligonucleotides, catalytic nucleic acids - ribozymes and deoxyribozymes - as well as small interfering RNAs (siRNAs). While antisense oligonucleotides were first used to identify an aspartyl protease with beta-secretase activity, all the strategies now demonstrate that siNAs are able to inhibit BACE gene expression in a sequence-specific manner, measured both at the level of its mRNA and at the level of protein. Moreover, knock-down of BACE reduces the intra- and extracellular population of Abeta40 and Abeta42 peptides. An anti-amyloid effect of siNAs is observed in a wide spectrum of cell lines as well as in primary cortical neurons. Thus targeting BACE with small inhibitory nucleic acids may be beneficial for the treatment of Alzheimer's disease and for future drug design.
journal_name
Acta Biochim Poljournal_title
Acta biochimica Polonicaauthors
Nawrot Bdoi
035001431subject
Has Abstractpub_date
2004-01-01 00:00:00pages
431-44issue
2eissn
0001-527Xissn
1734-154Xjournal_volume
51pub_type
杂志文章,评审abstract::The present paper investigates the enhancement of the therapeutic effect of Paclitaxel (a potent anticancer drug) by increasing its cellular uptake in the cancerous cells with subsequent reduction in its cytotoxic effects. To fulfill these goals the Paclitaxel (PTX)-Biotinylated PAMAM dendrimer complexes were prepared...
journal_title:Acta biochimica Polonica
pub_type: 杂志文章
doi:10.18388/abp.2017_2331
更新日期:2018-01-01 00:00:00
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journal_title:Acta biochimica Polonica
pub_type: 杂志文章
doi:
更新日期:1978-01-01 00:00:00
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journal_title:Acta biochimica Polonica
pub_type: 杂志文章
doi:10.18388/abp.2017_1570
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abstract::Human STAU1 is one member of the family of double-stranded RNA (dsRNA)-binding proteins. It is thought to function in transporting mRNA, controlling translation and eliciting mRNA decay in neurons, and to function in infection of influenza virus and human immunodeficiency virus type 1 (HIV-1). Four transcripts coding ...
journal_title:Acta biochimica Polonica
pub_type: 杂志文章
doi:
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abstract::The PCR conditions have been optimized to make the process faster and more economical. When short DNA fragments are to be amplified, the time of denaturation, annealing and extension steps can be as short as 1 s each, and the yield of PCR product is still high, sufficient for many types of analysis. The PCR can be don...
journal_title:Acta biochimica Polonica
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::Diabetes is one of the major challenges of modern medicine, as it is considered a global epidemic of the XXI century. The disease often leads to the development of serious, health threatening complications. Diabetic foot syndrome is a characteristic set of anatomical and molecular changes. At the macroscopic level, ma...
journal_title:Acta biochimica Polonica
pub_type: 杂志文章,评审
doi:
更新日期:2012-01-01 00:00:00
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journal_title:Acta biochimica Polonica
pub_type: 杂志文章,评审
doi:10.18388/abp.2018_2635
更新日期:2018-01-01 00:00:00
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journal_title:Acta biochimica Polonica
pub_type: 杂志文章
doi:
更新日期:1999-01-01 00:00:00
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journal_title:Acta biochimica Polonica
pub_type: 杂志文章
doi:10.18388/abp.2014_825
更新日期:2015-01-01 00:00:00
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journal_title:Acta biochimica Polonica
pub_type: 杂志文章
doi:10.18388/abp.2015_1013
更新日期:2016-01-01 00:00:00
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journal_title:Acta biochimica Polonica
pub_type: 杂志文章
doi:
更新日期:1980-01-01 00:00:00
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journal_title:Acta biochimica Polonica
pub_type: 杂志文章
doi:035001103
更新日期:2003-01-01 00:00:00
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journal_title:Acta biochimica Polonica
pub_type: 更正并重新发布的文章,杂志文章
doi:
更新日期:1991-01-01 00:00:00
abstract::1. A lytic enzyme was isolated from Vi phage III-induced lysate of Salmonella typhi, and purified about 200-fold by chromatography on IRC-50, CM-cellulose, and Sephadex G-75 columns. 2. Both E. coli B murein and muropeptide C6 were digested on incubation with the lytic enzyme. The main product of murein and muropeptid...
journal_title:Acta biochimica Polonica
pub_type: 杂志文章
doi:
更新日期:1975-01-01 00:00:00
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journal_title:Acta biochimica Polonica
pub_type: 杂志文章
doi:
更新日期:2002-01-01 00:00:00
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journal_title:Acta biochimica Polonica
pub_type: 杂志文章
doi:
更新日期:2002-01-01 00:00:00
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journal_title:Acta biochimica Polonica
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
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journal_title:Acta biochimica Polonica
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract::Isoelectric focusing of homogenous arylsulfatase B from human placenta pointed to the presence of enzymatically active and inactive forms of high pI (pH 9-8) and of lower pI (pH 6.5-5.5). Glycan chain analysis performed with the use of a Glycan Differentiation Kit showed that basic forms of arylsulfatase B from human ...
journal_title:Acta biochimica Polonica
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
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journal_title:Acta biochimica Polonica
pub_type: 杂志文章
doi:
更新日期:2002-01-01 00:00:00
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journal_title:Acta biochimica Polonica
pub_type: 杂志文章
doi:
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journal_title:Acta biochimica Polonica
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
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journal_title:Acta biochimica Polonica
pub_type: 杂志文章,评审
doi:
更新日期:2011-01-01 00:00:00
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journal_title:Acta biochimica Polonica
pub_type: 杂志文章,评审
doi:
更新日期:2002-01-01 00:00:00
abstract::The immunodiffusion cross-reactivity and competitive inhibition ELISA assays were used for immunological differentiation of latent form, cleaved form and guanidinium hydrochloride (GuHCl) induced polymer of human alpha 1-proteinase inhibitor (alpha 1-PI). Under the conditions studied, the differences between latent fo...
journal_title:Acta biochimica Polonica
pub_type: 杂志文章
doi:
更新日期:1996-01-01 00:00:00
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journal_title:Acta biochimica Polonica
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
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journal_title:Acta biochimica Polonica
pub_type: 杂志文章
doi:10.18388/abp.2019_2775
更新日期:2019-09-17 00:00:00
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journal_title:Acta biochimica Polonica
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
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journal_title:Acta biochimica Polonica
pub_type: 杂志文章
doi:0249041029
更新日期:2002-01-01 00:00:00
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journal_title:Acta biochimica Polonica
pub_type: 杂志文章,评审
doi:
更新日期:1996-01-01 00:00:00