Identification of the major Aβ1–42-degrading catabolic pathway in brain parenchyma: Suppression leads to biochemical and pathological deposition

By N. Iwata, S. Tsubuki, Y. Takaki, Kaori Watanabe, Misaki Sekiguchi, Emi Hosoki, Maho Kawashima-Morishima, Hahn‐Jun Lee, E. Hama, Yoko Sekine‐Aizawa and 1 more. Nature Medicine, 2000

899 citations recorded by the source corpus.

Subfields: Cellular and Molecular Neuroscience, Oncology, Physiology

View Paper: https://www.semanticscholar.org/paper/2e6228ce0727f4c6edc441af343a57e3c9e48e1f

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. Berislav Zlokovic
2. R. Deane
3. Mark P. Mattson
4. Ralph A. Nixon
5. P. Tontonoz
6. D. Holtzman
7. B. Lamb
8. Michael T. Heneka

In Oncology

1. Berislav Zlokovic
2. D. Holtzman
3. P. Tontonoz
4. N. Zelcer
5. Mark P. Mattson
6. R. Bell

In Physiology

1. Berislav Zlokovic
2. D. Holtzman
3. Mark P. Mattson
4. A. Sagare
5. R. Bell
6. R. Deane
7. A. Friedman
8. G. Bedi

Citations in the corpus

• Autophagy, amyloidogenesis and Alzheimer disease (2007, background): “The best-characterized proteases in this group are all zinc metallopeptidases: neprilysin (Iwata et al., 2000); insulindegrading enzyme (Kurochkin and Goto, 1994; McDermott and Gibson, 1997) and the endothelin-converting enzymes ECE1 and ECE2 (Eckman et al., 2001; Eckman et al., 2003).”
• The role of microglia in amyloid clearance from the AD brain (2010, methodology): “In addition to insulin, sAb has been reported to be the canonical substrate of IDE (Iwata et al. 2000).”
• Transport Pathways for Clearance of Human Alzheimer's Amyloid β-Peptide and Apolipoproteins E and J in the Mouse Central Nervous System (2007, background): “…Deane et al, 2003), binding of Ab to apolipoprotein E (apoE) (Martel et al, 1997) and apoJ (Zlokovic et al, 1996), Ab metabolism (Selkoe, 2001; Iwata et al, 2000, 2001), and degradation by astrocytes (Wyss-Coray et al, 2003; Koistinaho et al, 2004) may influence Ab transport exchange at the…”
• An Overview of APP Processing Enzymes and Products (2010, positive): “Aβ can be cleaved by proteases such as insulin degrading enzyme (Kurochkin and Goto, 1994), neprilysin (Iwata et al., 2000), BACE1 (Huse et al., 2002) and cathepsin B (only Aβ 1–42) (Mueller-Steiner et al. 2006).”
• ApoE promotes the proteolytic degradation of Abeta. (2008, background): “Ab peptides are proteolytically degraded within the brain principally by neprilysin (NEP) (Iwata et al., 2000) and insulin-degrading enzyme (IDE, insulysin) (Kurochkin and Goto, 1994).”
• Alzheimer’s Disease and the β-Amyloid Peptide (2010, neutral): “Two major enzymes, neprilysin (NEP) and insulin degrading enzyme (also known as insulysin; IDE), are believed responsible for most A β degradation [51–55].”
• Clearance of Alzheimer's amyloid-ss(1-40) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier. (2000, methodology): “However, the physiological relevance of the proposed degradation mechanism for Aβ1-42 (28) remains unclear, because the peptide was studied at extremely high concentrations (∼ 240 μM) that are not found even in brains with severe β-amyloidosis (30).”