摘要:
Methods and assays for detecting β-secretase (BACE-1) activity in body fluids or tissue extracts from individuals, particularly individuals who have Alzheimer's disease, are disclosed. A truncated form of BACE-1 was isolated that can be used as a biomarker for Alzheimer's disease.
摘要:
Provided are methods of identifying inhibitors of β-secretase that employ modified β-secretase substrates. The modified β-secretase substrates have β-secretase cleavage sites that are altered from wild type. The amino acid sequences of the altered β-secretase cleavage sites contain different amino acids in at least one of the positions P2-P1-P1′-P2′ of the β-secretase cleavage site. Many of the modified β-secretase substrates are more efficient substrates for β-secretase than are corresponding substrates having wild-type sequences, that is, these modified substrates are more susceptible to enzymatic breakdown by β-secretase. Recombinant polynucleotide molecules encoding the modified β-secretase substrates are provided. Antibodies that recognize cleavage products of the modified β-secretase substrates are provided. Stable cell lines expressing the modified β-secretase substrates are provided. Transgenic animals expressing the modified β-secretase substrates are provided.
摘要:
The present invention provides DNA constructs, genetically engineered host cells, and methods for identifying inhibitors of amyloid precursor protein (APP) processing. The methods provide for the convenient identification, in a single assay, of inhibitors of β-secretase and γ-secretase as well as other forms of APP processing. The methods rely on fusion proteins of APP and transcription factors in which APP processing releases the transcription factors, allowing the transcription factors to activate transcription of a reporter gene. Inhibitors are identified as substances that block or diminish transcription factor release from the fusion protein, thereby causing a diminution of reporter gene readout.
摘要:
A treatment device is provided for applying electrical energy to biological tissue in conjunction with injecting a composition that advantageously diffuses through the tissue. An injector such as a syringe has a reservoir for the treatment composition and injection cannula. The cannula can function as an electrode, and one or more additional electrodes are provided as opposed electrodes. The electrodes can each have tissue penetrating needles, or one or more of the electrodes can have a surface bearing conductive contact part. The syringe or other injector and a drive unit that applies electrical power to the electrodes are operable simultaneously or in a sequence, and can be triggered by switches or automatically upon detection of the injection proceeding to a predetermined state. The treatment device preferably uses a disposable syringe received in a carrier and generally is provided with a non-threatening appearance by minimizing tissue penetration and potential high voltage aspects.
摘要:
The present invention provides transgenic animals having an amyloid precursor protein wherein the amino acids flanking the &bgr; secretase cleavage site are NF and EV. The invention also provides tissues and cell lines derived from such animals. The invention further provides methods of screening candidate compounds to determine whether the compounds can alter the rate of cleavage of amyloid precursor protein by &bgr; secretase.
摘要:
An attachment locks a bicycle rack and/or a bicycle to a vehicle. The attachment may have a rigid body with a first end adapted to attach to a portion of the bicycle rack and/or a bicycle, and a second end adapted for insertion into a trunk or hatch space of the vehicle. The first end may include a loop, clasp or pivot joint which attaches to the bicycle or bicycle rack. The second end may be provided with an angle section joined to the rigid body via a radius. The second end is thin and flat, to allow the second end to extend into the trunk space and remain captured in the trunk space by a closed trunk lid, without interfering with operation of the trunk lid. An anchor may extend through or project outwardly from the second end, to resist attempts to pull the attachment out of the trunk space by force. A trunk bar has a loop section and ends adapted to be secured into a trunk space.