Microtubule stabilizing agents are among the most clinically useful chemotherapeutic drugs. Mostly, they act to stabilize microtubules and inhibit cell division. While not without side effects, new generations of these compounds display improved pharmacokinetic properties and brain penetrance. Neurological disorders are intrinsically associated with microtubule defects, and efforts to reposition microtubule-targeting chemotherapeutic agents for treatment of neurodegenerative and psychiatric illnesses are underway. Here we catalog microtubule regulators that are associated with Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis, schizophrenia and mood disorders. We outline the classes of microtubule stabilizing agents used for cancer treatment, their brain penetrance properties and neuropathy side effects, and describe efforts to apply these agents for treatment of brain disorders. Finally, we summarize the current state of clinical trials for microtubule stabilizing agents under evaluation for central nervous system disorders.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092511 | PMC |
http://dx.doi.org/10.3389/fncel.2018.00226 | DOI Listing |
PLoS One
December 2024
Department of Physics and Astronomy, The University of Texas at San Antonio, San Antonio, Texas, United States of America.
The accurate characterization of microtubules is essential for understanding their roles in various biological activities in eukaryotic cellular processes. In vitro, experimental data on these systems often need more details and information on sample preparation protocols and experimental techniques. This deficiency leads to unreproducible or contradictory outcomes.
View Article and Find Full Text PDFJ Mol Histol
December 2024
Grupo de Morfología Celular, Instituto Nacional de Salud (INS), Av. Calle 26 No. 51-20, Bogotá, DC, 111321, Colombia.
The effect of rabies virus infection on dendritic morphology and on the expression of the MAP2 protein in Purkinje cells in the cerebellum of mice was studied. ICR mice were inoculated with rabies virus, and six days later, the mice were sacrificed, the cerebellum was removed and processed for Golgi-Cox staining or MAP2 immunohistochemistry. Infection with rabies virus altered the dendritic pattern of Purkinje cells ranged from moderate changes to accentuated retraction in the dendritic tree of some Purkinje cells.
View Article and Find Full Text PDFOsteoarthritis Cartilage
December 2024
Department of Oral Anatomy and Physiology and TMD, College of Stomatology, the Fourth Military Medical University. Xi'an, China; Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Shanghai Stomatological Hospital, Fudan University, Shanghai, China. Electronic address:
Objective: Abnormal mechanical stress is intimately coupled with osteoarthritis (OA). Microtubules play a vital role in the regulation of mechanotransduction and intracellular transport. The purpose of the present study was to investigate the impact of stress-induced microtubule impairment on intracellular transport and lipid droplet (LD) accumulation in chondrocytes.
View Article and Find Full Text PDFJ Am Chem Soc
December 2024
Department of Chemical Sciences and Center for Advanced Functional Materials, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur 741246, West Bengal, India.
Triple-negative breast cancer (TNBC) poses significant treatment challenges due to its high metastasis, heterogeneity, and poor biomarker expression. The N-terminus of an octapeptide NAPVSIPQ () was covalently coupled to a carboxylic acid derivative of Ru(2,2'-bipy) () to synthesize an N-stapled short peptide-Rubpy conjugate (). This photosensitizer (PS) was utilized to treat TNBC through microtubule (MT) targeted chemotherapy and photodynamic therapy (PDT).
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
Guangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, China.
Aneuploidy eggs are a common cause of human infertility, spontaneous abortion, or trisomy syndromes. The spindle assembly checkpoint (SAC) plays a crucial role in preventing aneuploidy in oocytes, yet it is unclear if additional mechanisms exist to ensure oocyte adherence to this checkpoint. It is now revealed that the microtubule-associated protein NUSAP can prevent oocytes from evading the SAC and regulate the speed of the cell cycle.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!