Abstract
The accumulation of amyloid beta (Aβ) in the brain is believed to play a central role in the development and progression of Alzheimer’s disease. Revisions to the amyloid cascade hypothesis now acknowledge the dynamic equilibrium in which Aβ exists and the importance of enzymes involved in the production and breakdown of Aβ in maintaining healthy Aβ levels. However, while a wealth of pharmacological and immunological therapies are being generated to inhibit the Aβ-producing enzymes, β-site APP cleavage enzyme 1 and γ-secretase, the therapeutic potential of stimulating Aβ-degrading enzymes such as neprilysin, endothelin-converting enzyme-1 and insulin-degrading enzyme remains relatively unexplored. Recent evidence indicates that increasing Aβ degradation as opposed to inhibiting synthesis is a more effective strategy to prevent Aβ build-up. Therefore Aβ degrading enzymes have become valuable targets of therapy. In this review, we discuss the pathway of Aβ synthesis and clearance along with the opportunities they present for therapeutic intervention, the benefits of increasing the expression/activity of Aβ-degrading enzymes, and the untapped therapeutic potential of enzyme activation.
| Original language | English |
|---|---|
| Pages (from-to) | 1289-1296 |
| Number of pages | 8 |
| Journal | Neurochemical Research |
| Volume | 44 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 15 Jun 2019 |
Keywords
- Alzheimer’s disease
- Amyloid beta
- Amyloid beta degrading enzymes
- Endothelin-converting enzyme
- Neprilysin
Cite this
}
Powering Amyloid Beta Degrading Enzymes : A Possible Therapy for Alzheimer’s Disease. / Sikanyika, Nkumbu L.; Parkington, Helena C.; Smith, A. Ian; Kuruppu, Sanjaya.
In: Neurochemical Research, Vol. 44, No. 6, 15.06.2019, p. 1289-1296.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Powering Amyloid Beta Degrading Enzymes
T2 - A Possible Therapy for Alzheimer’s Disease
AU - Sikanyika, Nkumbu L.
AU - Parkington, Helena C.
AU - Smith, A. Ian
AU - Kuruppu, Sanjaya
PY - 2019/6/15
Y1 - 2019/6/15
N2 - The accumulation of amyloid beta (Aβ) in the brain is believed to play a central role in the development and progression of Alzheimer’s disease. Revisions to the amyloid cascade hypothesis now acknowledge the dynamic equilibrium in which Aβ exists and the importance of enzymes involved in the production and breakdown of Aβ in maintaining healthy Aβ levels. However, while a wealth of pharmacological and immunological therapies are being generated to inhibit the Aβ-producing enzymes, β-site APP cleavage enzyme 1 and γ-secretase, the therapeutic potential of stimulating Aβ-degrading enzymes such as neprilysin, endothelin-converting enzyme-1 and insulin-degrading enzyme remains relatively unexplored. Recent evidence indicates that increasing Aβ degradation as opposed to inhibiting synthesis is a more effective strategy to prevent Aβ build-up. Therefore Aβ degrading enzymes have become valuable targets of therapy. In this review, we discuss the pathway of Aβ synthesis and clearance along with the opportunities they present for therapeutic intervention, the benefits of increasing the expression/activity of Aβ-degrading enzymes, and the untapped therapeutic potential of enzyme activation.
AB - The accumulation of amyloid beta (Aβ) in the brain is believed to play a central role in the development and progression of Alzheimer’s disease. Revisions to the amyloid cascade hypothesis now acknowledge the dynamic equilibrium in which Aβ exists and the importance of enzymes involved in the production and breakdown of Aβ in maintaining healthy Aβ levels. However, while a wealth of pharmacological and immunological therapies are being generated to inhibit the Aβ-producing enzymes, β-site APP cleavage enzyme 1 and γ-secretase, the therapeutic potential of stimulating Aβ-degrading enzymes such as neprilysin, endothelin-converting enzyme-1 and insulin-degrading enzyme remains relatively unexplored. Recent evidence indicates that increasing Aβ degradation as opposed to inhibiting synthesis is a more effective strategy to prevent Aβ build-up. Therefore Aβ degrading enzymes have become valuable targets of therapy. In this review, we discuss the pathway of Aβ synthesis and clearance along with the opportunities they present for therapeutic intervention, the benefits of increasing the expression/activity of Aβ-degrading enzymes, and the untapped therapeutic potential of enzyme activation.
KW - Alzheimer’s disease
KW - Amyloid beta
KW - Amyloid beta degrading enzymes
KW - Endothelin-converting enzyme
KW - Neprilysin
UR - http://www.scopus.com/inward/record.url?scp=85062477224&partnerID=8YFLogxK
U2 - 10.1007/s11064-019-02756-x
DO - 10.1007/s11064-019-02756-x
M3 - Article
VL - 44
SP - 1289
EP - 1296
JO - Neurochemical Research
JF - Neurochemical Research
SN - 0364-3190
IS - 6
ER -