Neurochemical research, 2010-02, Vol.35 (2), p.181-210
2010
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Details
- Autor(en) / Beteiligte
- Titel
- BACE and γ-Secretase Characterization and Their Sorting as Therapeutic Targets to Reduce Amyloidogenesis
- Ist Teil von
- Neurochemical research, 2010-02, Vol.35 (2), p.181-210
- Ort / Verlag
- Boston: Springer US
- Erscheinungsjahr
- 2010
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Secretases are named for enzymes processing amyloid precursor protein (APP), a prototypic type-1 membrane protein. This led directly to discovery of novel Aspartyl proteases (β-secretases or BACE), a tetramer complex γ-secretase (γ-SC) containing presenilins , nicastrin, aph-1 and pen-2 , and a new role for metalloprotease(s) of the ADAM family as a α-secretases. Recent advances in defining pathways that mediate endosomal-lysosomal-autophagic-exosomal trafficking now provide targets for new drugs to attenuate abnormal production of fibril forming products characteristic of AD. A key to success includes not only characterization of relevant secretases but mechanisms for sorting and transport of key metabolites to abnormal vesicles or sites for assembly of fibrils. New developments we highlight include an important role for an ‘early recycling endosome’ coated in retromer complex containing lipoprotein receptor LRP-II (SorLA) for switching APP to a non-amyloidogenic pathway for α-secretases processing, or to shuttle APP to a ‘late endosome compartment’ to form Aβ or AICD. LRP11 (SorLA) is of particular importance since it decreases in sporadic AD whose etiology otherwise is unknown.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0364-3190eISSN: 1573-6903DOI: 10.1007/s11064-009-0054-1Titel-ID: cdi_proquest_miscellaneous_733795179
- Format
- –
- Schlagworte
- ADAM Proteins - physiology, Alzheimer Disease - physiopathology, Amino Acid Sequence, Amyloid - metabolism, Amyloid beta-Protein Precursor - metabolism, Amyloid Precursor Protein Secretases - antagonists & inhibitors, Amyloid Precursor Protein Secretases - genetics, Amyloid Precursor Protein Secretases - metabolism, Amyloid Precursor Protein Secretases - physiology, Animals, Aspartic Acid Endopeptidases - genetics, Aspartic Acid Endopeptidases - metabolism, Aspartic Acid Proteases - metabolism, Autophagy - physiology, Biochemistry, Biomedical and Life Sciences, Biomedicine, Cell Biology, Cerebral Amyloid Angiopathy - genetics, Cerebral Amyloid Angiopathy - physiopathology, Drug Design, Humans, Membrane Glycoproteins - physiology, Membrane Proteins - genetics, Membrane Proteins - physiology, Molecular Sequence Data, Neurochemistry, Neurology, Neurosciences, Overview, Peptide Hydrolases, Presenilins - genetics, Protein Structure, Tertiary, Signal Transduction - physiology, Substrate Specificity