γ-Secretase

Alzheimer's disease (AD) is a group of neurodegenerative diseases that manifest clinically as amyloid plaques in sections of brain tissue, progressive neuronal death, impaired cognition and memory, and gradual loss of brain function. The γ-secretase complex is composed of four membrane integral proteins, including Presenilin (PS1), Aph-1, Pen-2, and Nicastrin. More than 150 amino acid mutations have been identified on PS1 that are associated with AD. Therefore, it is not only of great scientific significance to resolve the three-dimensional structure of γ-secretase and understand its normal operation and pathogenesis based on it, but also will play an important role in guiding the development of drugs for AD.

Cryo-electron microscopy (Cryo-EM) technique enables direct observation of liquid, semi-liquid, and electron beam-sensitive samples, and has yielded remarkable results in biological and polymeric materials. This property provides important structural information for the study of AD-related γ-secretase inhibitors with substrate selectivity.

Creative Biostructure helps you perform γ-secretase studies by using high-resolution Cryo-EM technology to reveal how regulators and inhibitors inhibit substrate entry. This can provide an explanation for previous AD clinical drug failures and help customers design and optimize next-generation γ-secretase inhibitors and modulators. Ultimately, we expect Cryo-EM to provide more fundamental information for relevant drug discovery.

• Sample preparation of γ-secretase complexes.
• Cryo-EM data collection of γ-secretase complexes.
• High-resolution 3D structure determination of γ-secretase complexes.

To perform structure identification, the most critical step is to obtain γ-secretase complexes with high purity, homogeneous and stable chemical properties, and activity. Our extensive attempts and continuous modification and optimization of expression and purification methods have allowed us to overexpress and purify samples of the γ-secretase complex in mammalian cells using transient transfection techniques to meet the requirements of Cryo-EM analysis.

Creative Biostructure uses Cryo-EM technology in drug discovery to demonstrate the full process of γ-secretase binding of substrates to drugs, providing a precise blueprint for understanding the regulatory mechanism of γ-secretase activity. Please contact our staff to submit your research needs and let us help you resolve the structure of important complexes at atomic resolution.

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