Mechanisms of Fibril Formation and Cellular Response
Martha Skinner, John L. Berk, Lawreen H. Connors, David C. Seldin in XIth International Symposium on Amyloidosis, 2007
Fratta P, Engel WK, McFerrin J, Davies KJ, Lin SW, Askanas V.2005. Proteasome inhibition and aggresome formation in sporadic inclusion-body myositis and in amyloid-beta precursor protein-overexpressing cultured human muscle fibers. Am J Pathol. 167:517-526.
The relationship between HDAC6, CXCR3, and SIRT1 genes expression levels with progression of primary open-angle glaucoma
Published in Ophthalmic Genetics, 2018
Mateusz Siwak, Marcin Maślankiewicz, Alicja Nowak-Zduńczyk, Wioletta Rozpędek, Radosław Wojtczak, Katarzyna Szymanek, Marta Szaflik, Jerzy Szaflik, Jacek P. Szaflik, Ireneusz Majsterek
Histone deacetylase 6 (HDAC6) is a cytoplasmic enzyme involved in a variety of biological functions, including regulation gene expression, chromatin dynamics, and cell cycle progression (30,31). Furthermore, some studies have demonstrated that HDAC6 plays pivotal role in aggresomal misfolded protein degradation because it might bind to polyubiquitinated proteins and dynein proteins and recruiting specific protein to dynein motors to transport misfolded proteins to aggresomes (32). Accumulation of misfolded proteins is a prominent pathological feature in many neurodegenerative diseases (33). The protein aggregate formation is observed not only in neuronal cell, but also in oligodendrocytes. The ubiquitin-proteasome system and autophagy-lysosome pathway are the two most important mechanisms that degrade misfolded proteins. They transport and remove misfolded protein from the cytoplasm by dynein motors via the microtubule network to the aggresome (34).
A comparative safety review of histone deacetylase inhibitors for the treatment of myeloma
Published in Expert Opinion on Drug Safety, 2019
Guldane Cengiz Seval, Meral Beksac
A total of 18 HDACs have been defined and grouped into four classes [5]. Class I, II, and IV HDACs have Zn2+-linked acetylase domains, whereas class III HDACs have NAD+ linked domains. Class I HDACs include HDAC1-HDAC3 and HDAC8 that are predominantly localized in the nucleus and act on histone proteins and transcription factors. Class II HDACs include HDAC4-HDAC7, HDAC9, and HDAC10 acting primarily on non-histone proteins [6]. Furthermore, class II HDACs have two subgroups; class IIa (HDAC4, 5, 7, and 9) and class IIb (HDAC6 and 10). Class IIa HDACs share an N-terminal domain distinct from other HDAC classes. HDAC6 is a cytosolic microtubule-associated deacetylase that mediates trafficking of ubiquitinated misfolded proteins to the aggresome/autophagy pathway. Selective inhibition of HDAC6 stops aggresome formation, thence inhibiting the degradation leading to accumulation of misfolded proteins within cells. Class III HDACs are sirtuins (SIRT1, 2, 3, 4, 5, 6, and 7). In addition, these groups of HDACs differ from the other HDACs due to differences in their catalytic function and unrelated sequences. The only class IV HDAC is HDAC11, which shares sequence homology with the catalytic core regions of both class I and II enzymes, but does not have enough similarity otherwise to be placed in either class [7].
Guillain-Barré syndrome after bortezomib therapy in a child with relapsed acute lymphoblastic leukemia
Published in Pediatric Hematology and Oncology, 2022
Valeria Ceolin, Rosita Cenna, Francesca Resente, Manuela Spadea, Franca Fagioli, Nicoletta Bertorello
Peripheral neuropathy (PN) has been described in patients receiving bortezomib, which is predominantly sensory. Symptoms include paresthesia, numbness in distal areas, particularly the lower limbs, burning sensations, dysesthesias, sensory loss, reduced proprioception, vibratory sensation, reduction of deep tendon reflexes and autonomic skin innervation. Neuropathic pain has also been described and happens more frequently than with other neurotoxic drugs.14 PN usually appears after a number of cycles of treatment and is associated with dose accumulation, but symptoms may also appear after the first few doses; recent studies28 did not find a clear linear correlation between the cumulative dose or dose intensity and the severity of polyneuropathy, indicating that certain patients developed a severe polyneuropathy following a relatively low dose of BZM. The pathophysiology of bortezomib induced neuropathy is not completely clear yet. Experimental studies suggest that aggresome formation, endoplasmic reticulum stress, myotoxicity, microtubule stabilization, inflammatory response, and DNA damage could contribute to this neurotoxicity.29