TY - JOUR
T1 - PROTACs and Other Chemical Protein Degradation Technologies for the Treatment of Neurodegenerative Disorders
AU - Tomoshige, Shusuke
AU - Ishikawa, Minoru
N1 - Funding Information:
The work described in this minireview article was partially supported by Grants in Aid for Scientific Research from The Ministry of Education, Culture, Sports, Science and Technology, Japan, and the Japan Society for the Promotion of Science (KAKENHI Grant No. 17K19476 (M.I.), and 18H05502 (M.I.)), and The Uehara Memorial Foundation (201920310).
Publisher Copyright:
© 2020 Wiley-VCH GmbH
PY - 2021/2/15
Y1 - 2021/2/15
N2 - Neurodegenerative disorders (NDs) are a group of diseases that cause neural cell damage, leading to motility and/or cognitive dysfunctions. One of the causative agents is misfolded protein aggregates, which are considered as undruggable in terms of conventional tools, such as inhibitors and agonists/antagonists. Indeed, there is currently no FDA-approved drug for the causal treatment of NDs. However, emerging technologies for chemical protein degradation are opening up the possibility of selective elimination of target proteins through physiological protein degradation machineries, which do not depend on the functions of the target proteins. Here, we review recent efforts towards the treatment of NDs using chemical protein degradation technologies, and we briefly discuss the challenges and prospects.
AB - Neurodegenerative disorders (NDs) are a group of diseases that cause neural cell damage, leading to motility and/or cognitive dysfunctions. One of the causative agents is misfolded protein aggregates, which are considered as undruggable in terms of conventional tools, such as inhibitors and agonists/antagonists. Indeed, there is currently no FDA-approved drug for the causal treatment of NDs. However, emerging technologies for chemical protein degradation are opening up the possibility of selective elimination of target proteins through physiological protein degradation machineries, which do not depend on the functions of the target proteins. Here, we review recent efforts towards the treatment of NDs using chemical protein degradation technologies, and we briefly discuss the challenges and prospects.
KW - autophagy inducers
KW - drug discovery
KW - neurodegenerative disorders
KW - PROTACs
KW - protein degradation
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U2 - 10.1002/anie.202004746
DO - 10.1002/anie.202004746
M3 - Review article
C2 - 32410219
AN - SCOPUS:85089527299
SN - 1433-7851
VL - 60
SP - 3346
EP - 3354
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 7
ER -