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Recent years have witnessed rapid progress in the discovery of therapeutic proteins and peptides for the treatment of central nervous system (CNS) diseases. However, their clinical applications have been considerably hindered by challenges such as low biomembrane permeability, poor stability, short circulation time, and the formidable blood-brain barrier (BBB). Recently, substantial improvements have been made in understanding the dynamics of the BBB and developing efficient approaches for delivering proteins and peptides to the CNS, especially by using various nanoparticles. Herein, we present an overview of the up-to-date understanding of the BBB under physiological and pathological conditions, emphasizing their effects on brain drug delivery. We summarize advanced strategies and elucidate the underlying mechanisms for delivering proteins and peptides to the brain. We highlight the developments and applications of nanocarriers in treating CNS diseases via BBB crossing. We also provide critical opinions on the limitations and obstacles of the current strategies and put forward prospects for future research.
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http://dx.doi.org/10.1021/acsnano.4c06851 | DOI Listing |
Comput Biol Med
September 2025
Institute of Biotechnology, Department of Medical Biotechnology, SIMATS Engineering, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, 602105, Tamil Nadu, India. Electronic address:
Small humanin-like peptide-6 (SHLP6), is derived from the mitochondrial genome. The 3D structure of SHLP6 was evaluated using PEPstr, with homology modeling predicting a Cyt-C structure with a DOPE score of -645.717 and a GA341 score of 0.
View Article and Find Full Text PDFWomens Health (Lond)
September 2025
Worldwide Medical and Safety, Pfizer Inc, New York, NY, USA.
Background: Endometriosis symptoms have multifaceted manifestations, and there are few approved nonsurgical treatment options. Gonadotropin-releasing hormone (GnRH) agonists/antagonists for endometriosis vary on efficacy, safety profile, and out-of-pocket (OOP) cost, among other features.
Objectives: This study quantified the importance that women with endometriosis in the United States (US) placed on pain and non-pain features that differ among these medications.
Mol Ther
September 2025
Xi'an No. 1 Hospital, First Affiliated Hospital of Northwest University, School of Medicine, Xi'an, China; Key Laboratory of Resource Biology and Biotechnology of Western China, Ministry of Education; Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest University, Xi'an,
N6-methyladenosine (mA) modification, primarily regulated by methyltransferase-like protein 3 (METTL3), plays a pivotal role in RNA metabolism and leukemogenesis. However, the post-translational mechanisms governing METTL3 stability and function remain incompletely understood. Given the widespread occurrence of O-GlcNAcylation on nuclear and cytosolic proteins, we hypothesized that METTL3 might undergo O-GlcNAcylation, thereby influencing its stability and oncogenic function in myeloid malignancies.
View Article and Find Full Text PDFDrug Discov Today
September 2025
Department of Pharmaceutical and Artificial-Intelligence Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, Peptide & Protein Drug Research Cen
The landscape of allosteric drug discovery is undergoing a transformative shift, driven by the integration of three computational approaches: machine learning (ML), molecular dynamics (MD) simulations, and network theory. ML identifies potential allosteric sites from multidimensional biological datasets; MD simulations, empowered by enhanced sampling algorithms, reveal transient conformational states; and network analyses uncover communication pathways, further aiding in site identification. Their synergy enables rational allosteric modulator design.
View Article and Find Full Text PDFEur J Pharm Sci
September 2025
Department of Medicinal Chemistry, Uppsala University, SE-75123 Uppsala, Sweden. Electronic address:
Subcutaneous (SC) injection is the primary alternative to oral administration for therapeutic proteins and peptides. However, bioavailability and absorption rate are often variable and difficult to predict. Therefore, there is a need for new biorelevant and predictive SC in vitro methods.
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