https://pubmed.ncbi.nlm.nih.gov/31522889/
Microtubules are critical for the extension of oligodendrocyte processes and myelin deposition, yet our knowledge of their microtubule biogenesis is limited. In this issue of Cell, Fu et al. (2019) identify an oligodendrocyte-enriched microtubule regulator that promotes microtubule growth from Golgi outposts and controls myelin sheath elongation, linking microtubule cytoarchitecture and myelination in the CNS.
Microtubules, Myelin Sheaths, and Altered Behavior
Tubulin Cytoskeleton in Neurodegenerative Diseases–not Only Primary Tubulinopathies
Searching for effective therapies for neurodegenerative diseases is undoubtedly necessary and urgent. This is, on the other hand, an extremely difficult task due to complex pathomechanisms of these diseases, their variabilities and different symptoms observed in patients. Moreover, ability of neurons to regenerate is extremely limited. Unfortunately, vast majority (if not all) of neurodegenerative diseases remain incurable (Pierzynowska et al. 2020).
Cytoskeleton with Special Emphasis on Microtubules
Cytoskeleton is a network of interlining filamentous proteins occurring in cytoplasm. It was assumed that it occurs solely in eukaryotic proteins, however, some 30 years ago, protein motifs homologous to actin (Bork et al. 1992) and both subunits of tubulin (α-tubulin and β-tubulin) (de Boer et al. 1992; RayChaudhuri and Park 1992; Mukherjee et al. 1993; Yutin and Koonin 2012) were discovered in bacteria and archea. Nevertheless, it is unlikely that the cytoskeleton of eukaryotic cells derives from prokaryotes, as detailed analyses indicated significant functional differences between components of cytoskeletal proteins occurring in eukaryotes and their bacterial structural analogs (Vesteg and Krajcovic 2008).
dysfunctions of mitochondria, leading to production of reactive oxygen species in cerebral endothelial cells. This can activate vascular inflammation that stimulates microglia and astrocytes, triggering the inflammatory cascade. As the inflammation becomes widespread, the blood–brain-barrier function is impaired, leading to neuroinflammation and further to neurodegeneration. In this light, it is important to note that recent review of medical data and analyses and experimental results led to the conclusion that the primary deleterious effects of P-tau are related to mitochondrial dysfunctions (Epremyan et al. 2022).
tau protein predominates in axons... This protein is normally associated with microtubules and promotes their assembly, as well as stabilizes these structures (physiological roles of tau have been reviewed recently by Liang et al. 2022). Due to alternative splicing of mRNA of the tau-encoding gene (the MAPT gene), there are 6 isoforms of the tau protein which differ in the length, ranging from 352 to 441 amino acid residues. These isoforms are classified as 3R (including 0N3R, 1N3R, and 2N3R isoforms) and 4R (including 0N4R, 1N4R, and 2N4R isoforms) groups
Definitely, P-tau contributes significantly to microtubule breakdown, while disrupted tubulin homeostasis facilitates tauopathy
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