A PIAS1 Protective Variant S510G Delays polyQ Disease Onset by Modifying Protein Homeostasis

2021 ◽  
Author(s):  
Yan Hua Lee ◽  
Yu‐Shuen Tsai ◽  
Che‐Chang Chang ◽  
Chun‐Chen Ho ◽  
Hsiu‐Ming Shih ◽  
...  
Keyword(s):  
Disease Onset ◽  
Protein Homeostasis ◽  
Polyq Disease ◽  
Protective Variant

Application of the Matthews's criteria to differentiate MS from NMOSD at disease onset in a Latin American cohort

2018 ◽  
Author(s):  
Edgar German Carnero Contentti ◽  
Juan Pablo Pettinicchi ◽  
Francisco Sanchez ◽  
Ibis Soto De Castillo
Keyword(s):  
Latin American ◽  
Disease Onset

Skeletal-Muscle Metabolic Reprogramming in ALS-SOD1 G93G Mice Predates Disease Onset and is a Promising Therapeutic Target

2019 ◽  
Author(s):  
Silvia Scaricamazza ◽  
Illari Salvatori ◽  
Giacomo Giacovazzo ◽  
Jean Philippe Loeffler ◽  
Frederique Renè ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Therapeutic Target ◽  
Disease Onset ◽  
Metabolic Reprogramming ◽  
Promising Therapeutic Target

Sam Domains in Multiple Diseases

2020 ◽  
Vol 27 (3) ◽  
pp. 450-476 ◽  
Author(s):  
Marian Vincenzi ◽  
Flavia Anna Mercurio ◽  
Marilisa Leone
Keyword(s):  
Disease Onset ◽  
Protein Domain ◽  
Sam Domain ◽  
Different Types ◽  
Protein Functions ◽  
Helical Protein ◽  
The Many ◽  
Novel Therapeutic Strategies ◽  
Novel Drug ◽  
Pathological Event

Background: The sterile alpha motif (Sam) domain is a small helical protein module, able to undergo homo- and hetero-oligomerization, as well as polymerization, thus forming different types of protein architectures. A few Sam domains are involved in pathological processes and consequently, they represent valuable targets for the development of new potential therapeutic routes. This study intends to collect state-of-the-art knowledge on the different modes by which Sam domains can favor disease onset and progression. Methods: This review was build up by searching throughout the literature, for: a) the structural properties of Sam domains, b) interactions mediated by a Sam module, c) presence of a Sam domain in proteins relevant for a specific disease. Results: Sam domains appear crucial in many diseases including cancer, renal disorders, cataracts. Often pathologies are linked to mutations directly positioned in the Sam domains that alter their stability and/or affect interactions that are crucial for proper protein functions. In only a few diseases, the Sam motif plays a kind of "side role" and cooperates to the pathological event by enhancing the action of a different protein domain. Conclusion: Considering the many roles of the Sam domain into a significant variety of diseases, more efforts and novel drug discovery campaigns need to be engaged to find out small molecules and/or peptides targeting Sam domains. Such compounds may represent the pillars on which to build novel therapeutic strategies to cure different pathologies.

Stew in its Own Juice: Protein Homeostasis Machinery Inhibition Reduces Cell Viability in Multiple Myeloma Cell Lines

2019 ◽  
Vol 19 (2) ◽  
pp. 112-119 ◽  
Author(s):  
Mariana B. de Oliveira ◽  
Luiz F.G. Sanson ◽  
Angela I.P. Eugenio ◽  
Rebecca S.S. Barbosa-Dantas ◽  
Gisele W.B. Colleoni
Keyword(s):  
Multiple Myeloma ◽  
Cell Death ◽  
Cell Viability ◽  
Cell Lines ◽  
Treatment Options ◽  
Compensatory Mechanism ◽  
Protein Homeostasis ◽  
Protein Response ◽  
Rpmi 8226

Introduction:Multiple myeloma (MM) cells accumulate in the bone marrow and produce enormous quantities of immunoglobulins, causing endoplasmatic reticulum stress and activation of protein handling machinery, such as heat shock protein response, autophagy and unfolded protein response (UPR).Methods:We evaluated cell lines viability after treatment with bortezomib (B) in combination with HSP70 (VER-15508) and autophagy (SBI-0206965) or UPR (STF- 083010) inhibitors.Results:For RPMI-8226, after 72 hours of treatment with B+VER+STF or B+VER+SBI, we observed 15% of viable cells, but treatment with B alone was better (90% of cell death). For U266, treatment with B+VER+STF or with B+VER+SBI for 72 hours resulted in 20% of cell viability and both treatments were better than treatment with B alone (40% of cell death). After both triplet combinations, RPMI-8226 and U266 presented the overexpression of XBP-1 UPR protein, suggesting that it is acting as a compensatory mechanism, in an attempt of the cell to handle the otherwise lethal large amount of immunoglobulin overload.Conclusion:Our in vitro results provide additional evidence that combinations of protein homeostasis inhibitors might be explored as treatment options for MM.

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