Abstract:
:Over two decades, γ-secretase has been the target for extensive therapeutic development due to its pivotal role in pathogenesis of Alzheimer's disease and cancer. However, it has proven to be a challenging task owing to its large set of substrates and our limited understanding of the enzyme's structural and mechanistic features. The scientific community is taking bigger strides towards solving this puzzle with recent advancement in techniques like cryogenic electron microscopy (cryo-EM) and photo-affinity labelling (PAL). This review highlights the significance of the PAL technique with multiple examples of photo-probes developed from γ-secretase inhibitors and modulators. The binding of these probes into active and/or allosteric sites of the enzyme has provided crucial information on the γ-secretase complex and improved our mechanistic understanding of this protease. Combining the knowledge of function and regulation of γ-secretase will be a decisive factor in developing novel γ-secretase modulators and biological therapeutics.
journal_name
Semin Cell Dev Bioljournal_title
Seminars in cell & developmental biologyauthors
Nie P,Vartak A,Li YMdoi
10.1016/j.semcdb.2020.03.002subject
Has Abstractpub_date
2020-09-01 00:00:00pages
43-53eissn
1084-9521issn
1096-3634pii
S1084-9521(18)30276-3journal_volume
105pub_type
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