Related Experiment Video
Updated: May 20, 2026
04:04
Transauricular Vagus Nerve Stimulation and Electroencephalographic Assessment in Disorders of Consciousness
Published on: July 11, 2025
PROTACs for central nervous system disorders: challenges and opportunities
Na Zheng1, Jikuan Shao1, Baichen Xiong1
1School of Pharmacy, China Pharmaceutical University, Nanjing 211198, People's Republic of China.
Bioorganic & Medicinal Chemistry
|May 18, 2026
Summary
Proteolysis-targeting chimeras (PROTACs) offer new hope for treating central nervous system (CNS) disorders by degrading disease-causing proteins. Researchers are overcoming challenges like blood-brain barrier (BBB) penetration to advance these novel therapeutics.
Area of Science:
- Neuroscience
- Pharmacology
- Biotechnology
Background:
- Central nervous system (CNS) disorders, including neurodegenerative diseases and brain tumors, present significant global health challenges.
- Current treatments offer limited efficacy, primarily focusing on symptomatic relief without halting disease progression.
Purpose of the Study:
- To provide a comprehensive overview of proteolysis-targeting chimeras (PROTACs) for CNS disorders.
- To highlight strategies for overcoming challenges in PROTAC development for CNS applications.
- To offer theoretical frameworks and strategic guidance for advancing protein degrader therapeutics in the CNS field.
Main Methods:
- Review of current research on PROTACs targeting CNS disorders.
- Analysis of strategies to enhance PROTAC degradation efficiency and blood-brain barrier (BBB) permeability.
- Synthesis of advances and challenges in the field.
Main Results:
- PROTACs show promise in degrading pathogenic proteins implicated in CNS disorders.
- Structural optimization and novel nano-delivery systems are improving PROTAC efficacy and BBB penetration.
- Preclinical research demonstrates significant potential for PROTACs in treating CNS disorders.
Conclusions:
- PROTACs represent a promising therapeutic strategy for CNS disorders, moving beyond symptomatic treatment.
- Overcoming challenges in degradation efficiency and BBB permeability is crucial for clinical translation.
- Continued research and strategic development are essential for realizing the full potential of PROTACs in CNS therapeutics.
Related Concept Videos
01:26Targets for Drug Action: Overview
Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
01:16Therapeutic Drug Monitoring: Overview and Classification
Therapeutic Drug Monitoring (TDM) is a clinical practice that measures specific drug levels in a patient's blood at designated intervals to ensure the drug concentration stays within a therapeutic range. This monitoring is crucial for optimizing individual dosage regimens, enhancing therapeutic efficacy, and minimizing drug-related toxicity. TDM is vital for drugs with narrow therapeutic windows, significant variability in pharmacokinetics, and a clear correlation between plasma levels and...
01:26Psychosis: Goals of Pharmacotherapy
Antipsychotic drugs are a crucial treatment method for acute and chronic psychoses, bipolar illness, and behavioral disorders. The selection of these drugs depends on several factors, including the state of the disease, clinical judgment, possible drug interactions, and the patient's sensitivity to adverse effects. In immediate scenarios, such as delirium and dementia, short-term treatment with low doses of high-potency typical or atypical agents can effectively manage symptom exacerbation. For...
01:21Pharmacodynamics: Overview and Principles
Pharmacodynamics is a scientific field that delves into drugs' intricate biochemical, cellular, and physiological effects on the human body. The study of pharmacodynamics helps us understand how drugs interact with the body and elicit various responses.
Most drugs' effects result from their interactions with drug receptors or targets within the body. These interactions trigger specific responses at the cellular or systemic level. Drug receptors can be found on the surfaces of cells or within...
Most drugs' effects result from their interactions with drug receptors or targets within the body. These interactions trigger specific responses at the cellular or systemic level. Drug receptors can be found on the surfaces of cells or within...
01:29Pharmacogenomics: Identification of New Drug Targets
Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
01:22CNS Stimulants: Psychedelic Agents
Hallucinogens, also known as psychedelic drugs, are a class of substances known for their ability to alter perception, cognition, and emotions. Despite their profound effects on the mind, these drugs are non-addictive, setting them apart from many other abused substances. The mechanism of action of these drugs lies in their impact on the 5-HT2A receptor in the brain. Upon activation, this receptor couples to Gq-type G proteins, triggering a cascade that releases intracellular calcium. This...