Targeted protein degradation (TPD) is an emerging strategy that is shifting drug discovery from functional inhibitors to proteolytic degraders. These therapeutic degraders can recruit disease-causing proteins to ubiquitin-proteasomal and endosome- lysosomal pathway for destruction. Various TDP modalities have been reported, including molecular glues, proteolysis targeting chimeras (PROTACs), lysosome-targeted chimeras (LYTACs), and specific and non-genetic inhibitor of apoptosis protein (IAP)-dependent protein erasers (SNIPERs). Currently, there are more than twenty degraders in clinical trials primarily for cancer treatment.
However, there are several obstacles in the discovery and development of Central Nervous System (CNS) disease-targeted therapy. First, neurons are post-mitotic cells and hardly used as culture models for drug studies. Secondly, the blood-brain barrier (BBB) prevents drugs from entering brain and reaching targeted proteins in neurons. Lastly, the degradation pathways for most CNS disease-causing proteins are still under investigation. As a result, only a few degraders have been reported targeting the proteins that cause neurological diseases.
To address these issues, this Research Topic will publish original research articles, full-length reviews, and mini-reviews in one of the following areas: a) CNS disease cell and organoid models, b) degradation pathways of CNS disease-causing proteins, c) BBB models for drug discovery, and d) CNS disease-targeted drug discovery. CNS disease-targeted drugs include TPD degraders as well as protein functional inhibitors.
Topic Editor Chunhai Hao is the co-founder and chairman of HB Therapeutics, Inc. and the co-founder, of Degrome Therapeutics, Inc. Anita Bellail is the co-founder and CEO of HB Therapeutics, Inc., and the co-founder, of Degrome Therapeutics, Inc. Jason Meyer receives grant funding from Sanofi Pharmaceuticals. The other Topic Editors declare no competing interests with regard to the Research Topic subject.
Keywords:
posttranslational modifications, UB, SUMO
Important Note:
All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
Targeted protein degradation (TPD) is an emerging strategy that is shifting drug discovery from functional inhibitors to proteolytic degraders. These therapeutic degraders can recruit disease-causing proteins to ubiquitin-proteasomal and endosome- lysosomal pathway for destruction. Various TDP modalities have been reported, including molecular glues, proteolysis targeting chimeras (PROTACs), lysosome-targeted chimeras (LYTACs), and specific and non-genetic inhibitor of apoptosis protein (IAP)-dependent protein erasers (SNIPERs). Currently, there are more than twenty degraders in clinical trials primarily for cancer treatment.
However, there are several obstacles in the discovery and development of Central Nervous System (CNS) disease-targeted therapy. First, neurons are post-mitotic cells and hardly used as culture models for drug studies. Secondly, the blood-brain barrier (BBB) prevents drugs from entering brain and reaching targeted proteins in neurons. Lastly, the degradation pathways for most CNS disease-causing proteins are still under investigation. As a result, only a few degraders have been reported targeting the proteins that cause neurological diseases.
To address these issues, this Research Topic will publish original research articles, full-length reviews, and mini-reviews in one of the following areas: a) CNS disease cell and organoid models, b) degradation pathways of CNS disease-causing proteins, c) BBB models for drug discovery, and d) CNS disease-targeted drug discovery. CNS disease-targeted drugs include TPD degraders as well as protein functional inhibitors.
Topic Editor Chunhai Hao is the co-founder and chairman of HB Therapeutics, Inc. and the co-founder, of Degrome Therapeutics, Inc. Anita Bellail is the co-founder and CEO of HB Therapeutics, Inc., and the co-founder, of Degrome Therapeutics, Inc. Jason Meyer receives grant funding from Sanofi Pharmaceuticals. The other Topic Editors declare no competing interests with regard to the Research Topic subject.
Keywords:
posttranslational modifications, UB, SUMO
Important Note:
All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.