ENTRIES A–Z
Philip Winn in Dictionary of Biological Psychology, 2003
Neurons, like other cells, are not simply formless bags of CYTOPLASM: they have a structure provided by the cytoskeleton—literally, the cell skeleton. The cytoskeletons of neurons have three principal components. MICROFILAMENTS are thin fibres made of two strands of the protein actin. Microfilaments are the most delicate element of the cytoskeleton and are found mostly lining the internal walls of membranes, helping maintain the positions of membrane-bound molecules (receptors, for instance). NEUROFILAMENTS are larger than microfilaments and provide general structural support. MICROTUBULES are hollow tubes formed by thirteen filaments made of the protein TUBULIN. Microtubules are involved in the transport of substances through the AXOPLASM. Alterations to the neuronal cytoskeleton have been thought to play a part in the process of LONG-TERM POTENTIATION.
Prolactin and the Regulation if Secretion Including Membrane Flow: Potential Roles for Tubulin and Microtubules*
James A. Rillema in Actions of Prolactin on Molecular Processes, 1987
Initiation of microtubule assembly in vivo may require special sites called microtubule organizing centers (MTOCs)84 which are associated with a variety of cell organelles such as membranes, the kinetochores of chromosomes, centrioles, or existing microtubules. Since physiological regulation of polymerization is determined to some extent by the level of unpolymerized tubulin available for assembly into microtubules, the factors governing tubulin synthesis are relevant to microtubule formation. Ben-Ze’ev et al.85 observed that when microtubules in cultured fibroblasts were depolymerized with colchicine or nocadazole, there was a rapid inhibition of tubulin synthesis and a reduction in the level of translatable tubulin mRNA. Vinblastine, which also disrupts microtubules, but leads to the aggregation of tubulin into large paracrystals without increasing free tubulin, resulted in an enhancement of tubulin synthesis rather than an inhibition.
Immunology of Scleroderma
Richard K. Burt, Alberto M. Marmont in Stem Cell Therapy for Autoimmune Disease, 2019
The centromere comprised of the kinetochore, which is a trilaminar disc-shaped structure, serves as the attachment site for the spindle microtubules. The microtubules facilitate the alignment and separation of the chromosome during mitosis.184,185 The prevalence of ACA in SSc varies but has been found to be strongly associated with the lcSSc.134 ACA has also been identified in normal individuals186 and patients with Raynaud’s,166,186 SLE,186 primary biliary cirrhosis,187 and morphea.187 ACA comprises at least 6 centromere polypeptides (CENP): CENP-A to CENP-F More than 90% of ACA-positive sera from SSc patients reacts with CENP-A, -B, and -C188 and studies have demonstrated that these antibodies are capable of disrupting mitosis.189 CENP-A is a protein that is very similar to histone H3 of the H3/H4 nucleosomal core and is approximately 18 kD in size. It copurifies with H3/H4, but it has a centromere specific binding domain and is therefore distinct from H3 and H4.190,191 CENP-B is a DNA binding protein of 80kD and can be identified in 100% of all ACA-positive sera. It is distributed throughout the centromeric alpha-satellite heterochromatin below the kinetochore.192 CENP-C is a 140 kD protein that is a component of the kinetochore plate, which is essential for normal centromere function.193
Investigation of the toxicological and inhibitory effects of some benzimidazole agents on acetylcholinesterase and butyrylcholinesterase enzymes
Published in Archives of Physiology and Biochemistry, 2021
Fikret Türkan
Benzimidazoles have been used for the last 30 years to control cereal-borne diseases. Some studies have also been reported that benzimidazoles have been used in controlling mycotoxin contamination caused by fungi (Chen et al.2007). GST enzymes are a multifunctional enzyme group that functions in cellular detoxification, and it catalyzes nonpolar compounds that contain electrophilic conjugates containing carbon, nitrogen, and sulfur atoms (Lacey 1990). The anthelmintic activities of the benzimidazoles are fully related to the active site of the coil in the tubulin in helminths of mammals. For this reason, benzimidazoles are selectively toxic to helminths which are parasites. Benzimidazoles drugs inhibit polymerization by affecting the metabolic energy, structure and integrity of the microtubule group of b-tubulinin which is found in parasite cells (Köhler 2001). Microtubules are cellular organs that play a vital role in cellular functions such as transport and mitosis. The degradation in the cell’s cytoplasm leads to impaired glucose uptake. As a result, the amount of stored glycogen is reduced. Thus, organelle deaths may result from the effects of drugs on cellular activities (Türkan et al.2018c, Türkan et al.2018d, Türkan et al.2019c).
Design, synthesis, and biological screening of a series of 4′-fluoro-benzotriazole-acrylonitrile derivatives as microtubule-destabilising agents (MDAs)
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Federico Riu, Roberta Ibba, Stefano Zoroddu, Simona Sestito, Michele Lai, Sandra Piras, Luca Sanna, Valentina Bordoni, Luigi Bagella, Antonio Carta
Cancer is one of the main clinical issues worldwide. Anticancer therapy is still a focus of academic and industrial research, which aims to improve the potency and safety of validated anticancer protocols and to create new ones.1 Antitumor compounds targeting the microtubule (MT) structure affect the cell skeleton and the replication process but also act on apoptosis, therefore some of them have been approved for clinical cancer treatment.2 Microtubules (MTs) have a fine-tuned dynamic mechanism of polymerisation and depolymerisation dealing with cell division. A single microtubule is constituted by heterodimers of α- and β-tubulin.3–5 Tubulin polymerisation is crucial for the creation of microtubules. It is regulated by the hydrolysis of GTP (guanosine-5′-triphosphate) in the β-portion of tubulin dimer. GTP caps stabilise the formed microtubule ends.6 The α- and β-hetero-polypeptides of tubulin have about 36–42% similarity to each other and each subunit consists of about 445 amino acids. The 3D structure of the α,β-tubulin heterodimer has been determined by X-ray diffraction (Protein Data Bank Identity [PDB ID]: 4O2B)7 and both monomers were shown to surround a GTP molecule. MT growth occurs at the plus end and the shortening at the minus end.8,9Figure 1 reports a simplified representation of the mitotic cycle and the microtubule depolymerisation at the plus end.
Therapeutic targets for the treatment of microsporidiosis in humans
Published in Expert Opinion on Therapeutic Targets, 2018
Bing Han, Louis M. Weiss
Microtubules are a characteristic feature of eukaryotic cells and critical in the formation of the mitotic spindle, cytoskeleton, flagella, and cilia. Microtubules are formed by polymerization of tubulin which is a dimeric protein composed of α-tubulin and β-tubulin (Figure 1(b)) [115]. Benzimidazoles are a heterocyclic aromatic organic compound which consists of the fusion of benzene and imidazole. These drugs are inhibitors of microtubule polymerization by binding to tubulin and disturbing the self-association of tubulin subunit [116,117]. The benzimidazoles include: albendazole, cambendazole, benomyl, carbendazim, fenbendazole, mebendazole, and triclabendazole. These compounds have diverse biological activity and applications including antifungal, anticancer, antihelminthic, antiviral, anti-histaminic, anti-inflammatory, anticoagulant properties, and antihypertensive effects [118,119]. They have been used since the 1960s as antihelminthic agents in veterinary and human medicine, and as antifungal agents in agriculture [115,120–124].