TY - JOUR
T1 - Targeted protein degradation for the treatment of Parkinson's disease
T2 - Advances and future perspective
AU - Amirian, Roshanak
AU - Badrbani, Mehdi Azadi
AU - Derakhshankhah, Hossein
AU - Izadi, Zhila
AU - Shahbazi, Mohammad Ali
N1 - Funding Information:
This work was supported by the Kermanshah University of Medical Sciences, Kermanshah, Iran.Dr. Shahbazi Acknowledges financial supports of the Incentive fund and Starterbeurs grant from the University of Groningen and University Medical Center Groningen.
Publisher Copyright:
© 2023 The Authors
PY - 2023/10
Y1 - 2023/10
N2 - Parkinson's disease (PD) is a progressive disorder that belongs to a class of neurodegenerative disorders (NDs) called Synucleinopathies. It has characterized by the misfolding and aggregation of a-synuclein. Our understanding of PD continues to evolve, and so does our approach to treatment. including therapies aimed at delaying pathology, quitting neuronal loss, and shortening the course of the disease by selectively targeting essential proteins suspected to play a role in PD pathogenesis. One emerging approach that is generating significant interest is Targeted Protein Degradation (TPD). TPD is an innovative method that allows us to specifically break down certain proteins using specially designed molecules or peptides, like PROteolysis-TArgeting-Chimera (PROTACs). This approach holds great promise, particularly in the context of NDs. In this review, we will briefly explain PD and its pathogenesis, followed by discussing protein degradation systems and TPD strategy in PD by reviewing synthesized small molecules and peptides. Finally, future perspectives and challenges in the field are discussed.
AB - Parkinson's disease (PD) is a progressive disorder that belongs to a class of neurodegenerative disorders (NDs) called Synucleinopathies. It has characterized by the misfolding and aggregation of a-synuclein. Our understanding of PD continues to evolve, and so does our approach to treatment. including therapies aimed at delaying pathology, quitting neuronal loss, and shortening the course of the disease by selectively targeting essential proteins suspected to play a role in PD pathogenesis. One emerging approach that is generating significant interest is Targeted Protein Degradation (TPD). TPD is an innovative method that allows us to specifically break down certain proteins using specially designed molecules or peptides, like PROteolysis-TArgeting-Chimera (PROTACs). This approach holds great promise, particularly in the context of NDs. In this review, we will briefly explain PD and its pathogenesis, followed by discussing protein degradation systems and TPD strategy in PD by reviewing synthesized small molecules and peptides. Finally, future perspectives and challenges in the field are discussed.
KW - Lewy bodies
KW - Parkinson's disease
KW - PROTAC
KW - Targeted protein degradation
KW - α-Synuclein
U2 - 10.1016/j.biopha.2023.115408
DO - 10.1016/j.biopha.2023.115408
M3 - Review article
AN - SCOPUS:85169063754
SN - 0753-3322
VL - 166
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
M1 - 115408
ER -