Advances in Drug Discovery Targeting Lysosomal Membrane Proteins
Open Access
- 17 April 2023
- journal article
- review article
- Published by MDPI AG in Pharmaceuticals
- Vol. 16 (4) , 601
Abstract
Lysosomes are essential organelles of eukaryotic cells and are responsible for various cellular functions, including endocytic degradation, extracellular secretion, and signal transduction. There are dozens of proteins localized to the lysosomal membrane that control the transport of ions and substances across the membrane and are integral to lysosomal function. Mutations or aberrant expression of these proteins trigger a variety of disorders, making them attractive targets for drug development for lysosomal disorder-related diseases. However, breakthroughs in R&D still await a deeper understanding of the underlying mechanisms and processes of how abnormalities in these membrane proteins induce related diseases. In this article, we summarize the current progress, challenges, and prospects for developing therapeutics targeting lysosomal membrane proteins for the treatment of lysosomal-associated diseases.Keywords
Funding Information
- National Natural Science Foundation of China (32070718, SZBL2021080601003, SKLRD-Z-202115)
- Shenzhen Bay Laboratory Open Fund Project (32070718, SZBL2021080601003, SKLRD-Z-202115)
- State Key Laboratory of Respiratory Disease (32070718, SZBL2021080601003, SKLRD-Z-202115)
- Guangzhou Key Medical Discipline Construction Project Fund (32070718, SZBL2021080601003, SKLRD-Z-202115)
This publication has 140 references indexed in Scilit:
- Heptahelical protein PQLC2 is a lysosomal cationic amino acid exporter underlying the action of cysteamine in cystinosis therapyProceedings of the National Academy of Sciences, 2012
- Phosphoinositide isoforms determine compartment-specific ion channel activityProceedings of the National Academy of Sciences, 2012
- Small molecule inhibitors reveal Niemann–Pick C1 is essential for Ebola virus infectionNature, 2011
- Ebola virus entry requires the cholesterol transporter Niemann–Pick C1Nature, 2011
- Lysosomal Proteolysis and Autophagy Require Presenilin 1 and Are Disrupted by Alzheimer-Related PS1 MutationsCell, 2010
- V-ATPase inhibitors and implication in cancer treatmentCancer Treatment Reviews, 2009
- NAADP mobilizes calcium from acidic organelles through two-pore channelsNature, 2009
- Evaluating the potential of Vacuolar ATPase inhibitors as anticancer agents and multigram synthesis of the potent salicylihalamide analog saliphenylhalamideBioorganic & Medicinal Chemistry Letters, 2008
- Neurologic, Gastric, and Opthalmologic Pathologies in a Murine Model of Mucolipidosis Type IVThe American Journal of Human Genetics, 2007
- SNAREs — engines for membrane fusionNature Reviews Molecular Cell Biology, 2006